2022/12/10 更新

写真a

ヨシマツ ヤスヒロ
吉松 康裕
YOSHIMATSU Yasuhiro
所属
教育研究院 医歯学系 医学系列 准教授
医歯学総合研究科 分子細胞医学専攻 シグナル伝達 准教授
職名
准教授
外部リンク

学位

  • 博士(医学) ( 2010年3月 )

  • 修士(農学) ( 2001年3月 )

研究キーワード

  • リンパ管

  • 骨形成因子

  • 内皮間葉移行

  • 血管新生

  • リンパ管新生

  • TGF-βファミリー

  • 血管

  • 腫瘍生物学

研究分野

  • ライフサイエンス / 分子生物学

  • ライフサイエンス / 応用生物化学

  • ライフサイエンス / 細胞生物学

  • ライフサイエンス / 医化学

経歴

  • 新潟大学   医歯学総合研究科 分子細胞医学専攻 シグナル伝達   准教授

    2019年5月 - 現在

学歴

  • 東京大学   大学院医学系研究科   病因・病理学専攻

    2006年4月 - 2010年3月

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  • 東京大学   大学院農学生命科学研究科   応用生命工学専攻

    1999年4月 - 2001年3月

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  • 東京大学   農学部

    1995年4月 - 1999年3月

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    国名: 日本国

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委員歴

  • 日本リンパ学会   評議員  

    2021年1月 - 現在   

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    団体区分:学協会

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  • 日本癌学会   評議員  

    2020年1月 - 現在   

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    団体区分:学協会

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  • 日本血管生物医学会   評議員  

    2014年4月 - 現在   

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    団体区分:学協会

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論文

  • Vasohibin-2 is required for epithelial-mesenchymal transition of ovarian cancer cells by modulating transforming growth factor-β signaling. 査読

    Norita R, Suzuki Y, Furutani Y, Takahashi K, Yoshimatsu Y, Podyma-Inoue KA, Watabe T, Sato Y

    Cancer science   108 ( 3 )   419 - 426   2017年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/cas.13157

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  • An analysis modality for vascular structures combining tissue-clearing technology and topological data analysis. 国際誌

    Kei Takahashi, Ko Abe, Shimpei I Kubota, Noriaki Fukatsu, Yasuyuki Morishita, Yasuhiro Yoshimatsu, Satoshi Hirakawa, Yoshiaki Kubota, Tetsuro Watabe, Shogo Ehata, Hiroki R Ueda, Teppei Shimamura, Kohei Miyazono

    Nature communications   13 ( 1 )   5239 - 5239   2022年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The blood and lymphatic vasculature networks are not yet fully understood even in mouse because of the inherent limitations of imaging systems and quantification methods. This study aims to evaluate the usefulness of the tissue-clearing technology for visualizing blood and lymphatic vessels in adult mouse. Clear, unobstructed brain/body imaging cocktails and computational analysis (CUBIC) enables us to capture the high-resolution 3D images of organ- or area-specific vascular structures. To evaluate these 3D structural images, signals are first classified from the original captured images by machine learning at pixel base. Then, these classified target signals are subjected to topological data analysis and non-homogeneous Poisson process model to extract geometric features. Consequently, the structural difference of vasculatures is successfully evaluated in mouse disease models. In conclusion, this study demonstrates the utility of CUBIC for analysis of vascular structures and presents its feasibility as an analysis modality in combination with 3D images and mathematical frameworks.

    DOI: 10.1038/s41467-022-32848-2

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  • Dose-response relationship of pulmonary disorders by inhalation exposure to cross-linked water-soluble acrylic acid polymers in F344 rats. 国際誌

    Tomoki Takeda, Shotaro Yamano, Yuko Goto, Shigeyuki Hirai, Yusuke Furukawa, Yoshinori Kikuchi, Kyohei Misumi, Masaaki Suzuki, Kenji Takanobu, Hideki Senoh, Misae Saito, Hitomi Kondo, George Daghlian, Young-Kwon Hong, Yasuhiro Yoshimatsu, Masanori Hirashima, Yoichiro Kobashi, Kenzo Okamoto, Takumi Kishimoto, Yumi Umeda

    Particle and fibre toxicology   19 ( 1 )   27 - 27   2022年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: In Japan, six workers handling cross-linked water-soluble acrylic acid polymer (CWAAP) at a chemical plant suffered from lung diseases, including fibrosis, interstitial pneumonia, emphysema, and pneumothorax. We recently demonstrated that inhalation of CWAAP-A, one type of CWAAP, causes pulmonary disorders in rats. It is important to investigate dose-response relationships and recoverability from exposure to CWAAPs for establishing occupational health guidelines, such as setting threshold limit value for CWAAPs in the workplace. METHODS: Male and female F344 rats were exposed to 0.3, 1, 3, or 10 mg/m3 CWAAP-A for 6 h/day, 5 days/week for 13 weeks using a whole-body inhalation exposure system. At 1 h, 4 weeks, and 13 weeks after the last exposure the rats were euthanized and blood, bronchoalveolar lavage fluid, and all tissues including lungs and mediastinal lymph nodes were collected and subjected to biological and histopathological analyses. In a second experiment, male rats were pre-treated with clodronate liposome or polymorphonuclear leukocyte-neutralizing antibody to deplete macrophages or neutrophils, respectively, and exposed to CWAAP-A for 6 h/day for 2 days. RESULTS: CWAAP-A exposure damaged only the alveoli. The lowest observed adverse effect concentration (LOAEC) was 1 mg/m3 and the no observed adverse effect concentration (NOAEC) was 0.3 mg/m3. Rats of both sexes were able to recover from the tissue damage caused by 13 weeks exposure to 1 mg/m3 CWAAP-A. In contrast, tissue damage caused by exposure to 3 and 10 mg/m3 was irreversible due to the development of interstitial lung lesions. There was a gender difference in the recovery from CWAAP-A induced pulmonary disorders, with females recovering less than males. Finally, acute lung effects caused by CWAAP-A were significantly reduced by depletion of alveolar macrophages. CONCLUSIONS: Pulmonary damage caused by inhalation exposure to CWAAP-A was dose-dependent, specific to the lung and lymph nodes, and acute lung damage was ameliorated by depleting macrophages in the lungs. CWAAP-A had both a LOAEC and a NOAEC, and tissue damage caused by exposure to 1 mg/m3 CWAAP-A was reversible: recovery in female rats was less than for males. These findings indicate that concentration limits for CWAAPs in the workplace can be determined.

    DOI: 10.1186/s12989-022-00468-9

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  • Emerging roles of inflammation-mediated endothelial-mesenchymal transition in health and disease. 国際誌

    Yasuhiro Yoshimatsu, Tetsuro Watabe

    Inflammation and regeneration   42 ( 1 )   9 - 9   2022年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Endothelial-mesenchymal transition (EndoMT), a cellular differentiation process in which endothelial cells (ECs) lose their properties and differentiate into mesenchymal cells, has been observed not only during development but also in various pathological states in adults, including cancer progression and organ/tissue fibrosis. Transforming growth factor-β (TGF-β), an inflammation-related cytokine, has been shown to play central roles in the induction of EndoMT. TGF-β induces EndoMT by regulating the expression of various transcription factors, signaling molecules, and cellular components that confer ECs with mesenchymal characteristics. However, TGF-β by itself is not necessarily sufficient to induce EndoMT to promote the progression of EndoMT-related diseases to a refractory extent. In addition to TGF-β, additional activation by other inflammatory factors is often required to stabilize the progression of EndoMT. Since recent lines of evidence indicate that inflammatory signaling molecules act as enhancers of EndoMT, we summarize the roles of inflammatory factors in the induction of EndoMT and related diseases. We hope that this review will help to develop therapeutic strategies for EndoMT-related diseases by targeting inflammation-mediated EndoMT.

    DOI: 10.1186/s41232-021-00186-3

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  • Construction of transplantable artificial vascular tissue based on adipose tissue-derived mesenchymal stromal cells by a cell coating and cryopreservation technique. 国際誌

    Yoshiya Asano, Daisuke Okano, Michiya Matsusaki, Tetsuro Watabe, Yasuhiro Yoshimatsu, Mitsuru Akashi, Hiroshi Shimoda

    Scientific reports   11 ( 1 )   17989 - 17989   2021年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Prevascularized artificial three-dimensional (3D) tissues are effective biomaterials for regenerative medicine. We have previously established a scaffold-free 3D artificial vascular tissue from normal human dermal fibroblasts (NHDFs) and umbilical vein-derived endothelial cells (HUVECs) by layer-by-layer cell coating technique. In this study, we constructed an artificial vascular tissue constructed by human adipose tissue-derived stromal cells (hASCs) and HUVECs (ASCVT) by a modified technique with cryopreservation. ASCVT showed a higher thickness with more dense vascular networks than the 3D tissue based on NHDFs. Correspondingly, 3D-cultured ASCs showed higher expression of several angiogenesis-related factors, including vascular endothelial growth factor-A and hepatic growth factor, compared to that of NHDFs. Moreover, perivascular cells in ASCVT were detected by pericyte markers, suggesting the differentiation of hASCs into pericyte-like cells. Subcutaneous transplantation of ASCVTs to nude mice resulted in an engraftment with anastomosis of host's vascular structures at 2 weeks after operation. In the engrafted tissue, the vascular network was surrounded by mural-like structure-forming hASCs, in which some parts developed to form vein-like structures at 4 weeks, suggesting the generation of functional vessel networks. These results demonstrated that cryopreserved human cells, including hASCs, could be used directly to construct the artificial transplantable tissue for regenerative medicine.

    DOI: 10.1038/s41598-021-97547-2

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  • Isolation and characterisation of lymphatic endothelial cells from lung tissues affected by lymphangioleiomyomatosis. 査読 国際誌

    Koichi Nishino, Yasuhiro Yoshimatsu, Tomoki Muramatsu, Yasuhito Sekimoto, Keiko Mitani, Etsuko Kobayashi, Shouichi Okamoto, Hiroki Ebana, Yoshinori Okada, Masatoshi Kurihara, Kenji Suzuki, Johji Inazawa, Kazuhisa Takahashi, Tetsuro Watabe, Kuniaki Seyama

    Scientific reports   11 ( 1 )   8406 - 8406   2021年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Lymphangioleiomyomatosis (LAM) is a rare pulmonary disease characterised by the proliferation of smooth muscle-like cells (LAM cells), and an abundance of lymphatic vessels in LAM lesions. Studies reported that vascular endothelial growth factor-D (VEGF-D) secreted by LAM cells contributes to LAM-associated lymphangiogenesis, however, the precise mechanisms of lymphangiogenesis and characteristics of lymphatic endothelial cells (LECs) in LAM lesions have not yet been elucidated. In this study, human primary-cultured LECs were obtained both from LAM-affected lung tissues (LAM-LECs) and normal lung tissues (control LECs) using fluorescence-activated cell sorting (FACS). We found that LAM-LECs had significantly higher ability of proliferation and migration compared to control LECs. VEGF-D significantly promoted migration of LECs but not proliferation of LECs in vitro. cDNA microarray and FACS analysis revealed the expression of vascular endothelial growth factor receptor (VEGFR)-3 and integrin α9 were elevated in LAM-LECs. Inhibition of VEGFR-3 suppressed proliferation and migration of LECs, and blockade of integrin α9 reduced VEGF-D-induced migration of LECs. Our data uncovered the distinct features of LAM-associated LECs, increased proliferation and migration, which may be due to higher expression of VEGFR-3 and integrin α9. Furthermore, we also found VEGF-D/VEGFR-3 and VEGF-D/ integrin α9 signaling play an important role in LAM-associated lymphangiogenesis.

    DOI: 10.1038/s41598-021-88064-3

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  • ASK1 suppresses NK cell‐mediated intravascular tumor cell clearance in lung metastasis 査読

    Makoto Fujimoto, Miki Kamiyama, Kosuke Fuse, Hiroki Ryuno, Takeru Odawara, Natsuki Furukawa, Yasuhiro Yoshimatsu, Tetsuro Watabe, Michaela Prchal‐Murphy, Veronika Sexl, Hideaki Tahara, Yoshihiro Hayakawa, Takehiro Sato, Kohsuke Takeda, Isao Naguro, Hidenori Ichijo

    Cancer Science   112 ( 4 )   1633 - 1643   2021年3月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    Tumor metastasis is the leading cause of death worldwide and involves an extremely complex process composed of multiple steps. Our previous study demonstrated that apoptosis signal-regulating kinase 1 (ASK1) deficiency in mice attenuates tumor metastasis in an experimental lung metastasis model. However, the steps of tumor metastasis regulated by ASK1 remain unclear. Here, we showed that ASK1 deficiency in mice promotes natural killer (NK) cell-mediated intravascular tumor cell clearance in the initial hours of metastasis. In response to tumor inoculation, ASK1 deficiency upregulated immune response-related genes, including interferon-gamma (IFNγ). We also revealed that NK cells are required for these anti-metastatic phenotypes. ASK1 deficiency augmented cytokine production chemoattractive to NK cells possibly through induction of the ligand for NKG2D, a key activating receptor of NK cells, leading to further recruitment of NK cells into the lung. These results indicate that ASK1 negatively regulates NK cell-dependent anti-tumor immunity and that ASK1-targeted therapy can provide a new tool for cancer immunotherapy to overcome tumor metastasis.

    DOI: 10.1111/cas.14842

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    その他リンク: https://onlinelibrary.wiley.com/doi/full-xml/10.1111/cas.14842

  • Targeting all transforming growth factor-β isoforms with a Fc chimeric receptor impairs tumor growth and angiogenesis of oral squamous cell cancer 査読

    Takahashi K, Akatsu Y, Podyma-Inoue KA, Matsumoto T, Takahashi H, Yoshimatsu Y, Koinuma D, Shirouzu M, Miyazono K, Watabe T

    Journal of Biological Chemistry   2020年12月

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  • TNF-α enhances TGF-β-induced endothelial-to-mesenchymal transition via TGF-β signal augmentation. Cancer Science 査読

    Yoshimatsu Y, Wakabayashi I, Kimuro S, Takahashi N, Takahashi K, Kobayashi M, Maishi N, Podyma-Inoue KA, Hida K, Miyazono K, Watabe T

    Cancer Science   111 ( 7 )   2385 - 2399   2020年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/cas.14455

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    その他リンク: https://onlinelibrary.wiley.com/doi/full-xml/10.1111/cas.14455

  • Peptide‐2 from mouse myostatin precursor protein alleviates muscle wasting in cancer‐associated cachexia 査読

    Ojima C, Noguchi Y, Miyamoto T, Saito Y, Orihashi H, Yoshimatsu Y, Watabe T, Takayama K, Hayashi Y, Itoh F

    Cancer Science   2020年6月

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  • TGF-β and TNF-α cooperatively induce mesenchymal transition of lymphatic endothelial cells via activation of Activin signals 査読

    *Yoshimatsu Y, *Kimuro S, Pauty J, Takagaki K, Nomiyama S, Inagawa A, Maeda K, Podyma-InoueKA, Kajiya K, Matsunaga Y, Watabe T

    PLoS One   15 ( 5 )   2020年5月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1371/journal.pone.0232356

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  • 線維芽細胞増殖因子(FGF2)は腫瘍血管内皮細胞においてTGF-βによって誘導される内皮-筋線維芽移行を制御する(Fibroblast growth factor 2 regulates TGF-β-induced endothelial-to-myofibroblast transition of tumor endothelial cells)

    吉松 康裕, 赤津 裕一, 高橋 直也, 紀室 志織, 村松 智輝, 桂 彰宏, 間石 奈湖, 鈴木 洋, 稲澤 譲治, 樋田 京子, 宮園 浩平, 渡部 徹郎

    日本癌学会総会記事   78回   P - 2280   2019年9月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • Fibroblast growth factor signals regulate transforming growth factor-β-induced endothelial-to-myofibroblast transition of tumor endothelial cells via Elk1 査読

    *Akatsu Y, *Takahashi N, *Yoshimatsu Y, Kimuro S, Muramatsu T, Katsura A, Maishi N, Suzuki HI, Inazawa J, Hida K, Miyazono K, Watabe T

    Molecular Oncology   2019年5月

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    担当区分:筆頭著者  

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  • Interleukin-13 receptor α2 is a novel marker and potential therapeutic target for human melanoma 査読

    *Okamoto H, *Yoshimatsu Y, *Tomizawa T, *Kunita A, *Takayama A, Morikawa T, Komura D, Takahashi K, Oshima T, Sato M, Komai M, Podyma-Inoue KA, Uchida H, Hamada H, Fujiu K, Ishikawa S, Fukayama M, Fukuhara T, Watabe T

    Scientific Reports   9 ( 1281 )   2019年1月

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    担当区分:筆頭著者  

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  • Regulatory role of transforming growth factor-β signals in the migration and tumor formation of HOC313-LM cells, an oral squamous cell carcinoma 査読

    Takahashi K, Podyma-Inoue KA, Takao C, Yoshimatsu Y, Muramatsu T, Inazawa J, Watabe T

    The Journal of the Stomatological Society   85 ( 2 )   52 - 61   2018年

  • Dual targeting of vascular endothelial growth factor and bone morphogenetic protein-9/10 impairs tumor growth through inhibition of angiogenesis 査読

    Yuichi Akatsu, Yasuhiro Yoshimatsu, Taishi Tomizawa, Kazuki Takahashi, Akihiro Katsura, Kohei Miyazono, Tetsuro Watabe

    CANCER SCIENCE   108 ( 1 )   151 - 155   2017年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Clinical development of anti-angiogenic agents has been a major landmark in cancer therapy for several types of cancers. Signals mediated by both vascular endothelial growth factor (VEGF) and bone morphogenetic protein (BMP)-9 and 10 have been implicated in tumor angiogenesis. However, previous studies have shown that targeting the individual signals was not sufficiently effective in retarding tumor growth in certain preclinical and clinical conditions. In the present study, we developed a novel decoy chimeric receptor that traps both VEGF and BMP-9/10. Single targeting of either VEGF or BMP-9/10 signals significantly reduced the formation of tumor vessels in a mouse xenograft model of human pancreatic cancer; however, it did not show significant therapeutic effects on tumor growth. In contrast, dual targeting of the angiogenic signals resulted in more significant inhibition of tumor angiogenesis, leading to delay of tumor growth. Our findings suggest that simultaneous blockade of VEGF and BMP-9/10 signals is a promising therapeutic strategy for the cancers that are resistant to anti-VEGF and BMP-9/10 therapies.

    DOI: 10.1111/cas.13103

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  • Roles of signaling and transcriptional networks in pathological lymphangiogenesis 査読

    Yasuhiro Yoshimatsu, Hideki Miyazaki, Tetsuro Watabe

    ADVANCED DRUG DELIVERY REVIEWS   99 ( Pt B )   161 - 171   2016年4月

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    担当区分:筆頭著者   記述言語:英語   出版者・発行元:ELSEVIER SCIENCE BV  

    Lymphangiogenesis, the generation of new lymphatic vessels, plays important roles in cancer metastasis. Outstanding progress during the past decade has dramatically increased the novel knowledge and insights of the mechanisms underlying the generation of new lymphatic vessels, the roles of transcription factors and lymphangiogenic growth factors during physiological development and pathological processes such as cancer and inflammation. Furthermore, an understanding of the molecular consequences during tumor lymphangiogenesis has provided chances to develop better diagnostic and therapeutic approaches that aim to limit the progression of cancer. In this article, we will explain the current knowledge of how lymphatic function is altered in various pathological conditions including cancer progression. (C) 2016 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.addr.2016.01.020

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  • Expression of platelet-derived growth factor receptor β is maintained by Prox1 in lymphatic endothelial cells and is required for tumor lymphangiogenesis. 査読

    *Miyazaki H, *Yoshimatsu Y, Akatsu Y, Mishima K, Fukayama M, Watabe T, Miyazono K

    Cancer science   105 ( 9 )   1116 - 1123   2014年9月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/cas.12476

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  • Bone morphogenetic protein-9 inhibits lymphatic vessel formation via activin receptor-like kinase 1 during development and cancer progression 査読

    Yasuhiro Yoshimatsu, Yulia G. Lee, Yuichi Akatsu, Luna Taguchi, Hiroshi I. Suzuki, Sara I. Cunha, Kazuichi Maruyama, Yuka Suzuki, Tomoko Yamazaki, Akihiro Katsura, S. Paul Oh, Teresa A. Zimmers, Se-Jin Lee, Kristian Pietras, Gou Young Koh, Kohei Miyazono, Tetsuro Watabe

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   110 ( 47 )   18940 - 18945   2013年11月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATL ACAD SCIENCES  

    Lymphatic vessels (LVs) play critical roles in the maintenance of fluid homeostasis and in pathological conditions, including cancer metastasis. Although mutations in ALK1, a member of the transforming growth factor (TGF)-beta/bone morphogenetic protein (BMP) receptor family, have been linked to hereditary hemorrhagic telangiectasia, a human vascular disease, the roles of activin receptor-like kinase 1(ALK-1) signals in LV formation largely remain to be elucidated. We show that ALK-1 signals inhibit LV formation, and LVs were enlarged in multiple organs in Alk1-depleted mice. These inhibitory effects of ALK-1 signaling were mediated by BMP-9, which decreased the number of cultured lymphatic endothelial cells. Bmp9-deficient mouse embryos consistently exhibited enlarged dermal LVs. BMP-9 also inhibited LV formation during inflammation and tumorigenesis. BMP-9 downregulated the expression of the transcription factor prospero-related homeobox 1, which is necessary to maintain lymphatic endothelial cell identity. Furthermore, silencing prospero-related homeobox 1 expression inhibited lymphatic endothelial cell proliferation. Our findings reveal a unique molecular basis for the physiological and pathological roles of BMP-9/ALK-1 signals in LV formation.

    DOI: 10.1073/pnas.1310479110

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  • TGF-β-induced mesenchymal transition of MS-1 endothelial cells requires Smad-dependent cooperative activation of Rho signals and MRTF-A. 査読

    Mihira H, Suzuki HI, Akatsu Y, Yoshimatsu Y, Igarashi T, Miyazono K, Watabe T

    Journal of biochemistry   151 ( 2 )   145 - 156   2012年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1093/jb/mvr121

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  • Ets family members induce lymphangiogenesis through physical and functional interaction with Prox1 査読

    Yasuhiro Yoshimatsu, Tomoko Yamazaki, Hajime Mihira, Taichi Itoh, Junichi Suehiro, Keiko Yuki, Kaori Harada, Masato Morikawa, Caname Iwata, Takashi Minami, Yasuyuki Morishita, Tatsuhiko Kodama, Kohei Miyazono, Tetsuro Watabe

    JOURNAL OF CELL SCIENCE   124 ( 16 )   2753 - 2762   2011年8月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:COMPANY OF BIOLOGISTS LTD  

    Prox1 plays pivotal roles during embryonic lymphatic development and maintenance of adult lymphatic systems by modulating the expression of various lymphatic endothelial cell (LEC) markers, such as vascular endothelial growth factor receptor 3 (VEGFR3). However, the molecular mechanisms by which Prox1 transactivates its target genes remain largely unknown. Here, we identified Ets-2 as a candidate molecule that regulates the functions of Prox1. Whereas Ets-2 has been implicated in angiogenesis, its roles during lymphangiogenesis have not yet been elucidated. We found that endogenous Ets-2 interacts with Prox1 in LECs. Using an in vivo model of chronic aseptic peritonitis, we found that Ets-2 enhanced inflammatory lymphangiogenesis, whereas a dominant-negative mutant of Ets-1 suppressed it. Ets-2 also enhanced endothelial migration towards VEGF-C through induction of expression of VEGFR3 in collaboration with Prox1. Furthermore, we found that both Prox1 and Ets-2 bind to the VEGFR3 promoter in intact chromatin. These findings suggest that Ets family members function as transcriptional cofactors that enhance Prox1-induced lymphangiogenesis.

    DOI: 10.1242/jcs.083998

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  • Roles of TGF-β signals in endothelial-mesenchymal transition during cardiac fibrosis. 査読

    Yoshimatsu Y, Watabe T

    International journal of inflammation   2011   724080   2011年

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    担当区分:筆頭著者  

    DOI: 10.4061/2011/724080

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  • Identification of targets of Prox1 during in vitro vascular differentiation from embryonic stem cells: functional roles of HoxD8 in lymphangiogenesis. 国際誌

    Kaori Harada, Tomoko Yamazaki, Caname Iwata, Yasuhiro Yoshimatsu, Hitoshi Sase, Koichi Mishima, Yasuyuki Morishita, Masanori Hirashima, Yuichi Oike, Toshio Suda, Naoyuki Miura, Tetsuro Watabe, Kohei Miyazono

    Journal of cell science   122 ( Pt 21 )   3923 - 30   2009年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    During lymphatic development, Prox1 plays central roles in the differentiation of blood vascular endothelial cells (BECs) into lymphatic endothelial cells (LECs), and subsequently in the maturation and maintenance of lymphatic vessels. However, the molecular mechanisms by which Prox1 elicits these functions remain to be elucidated. Here, we identified FoxC2 and angiopoietin-2 (Ang2), which play important roles in the maturation of lymphatic vessels, as novel targets of Prox1 in mouse embryonic-stem-cell-derived endothelial cells (MESECs). Furthermore, we found that expression of HoxD8 was significantly induced by Prox1 in MESECs, a finding confirmed in human umbilical vein endothelial cells (HUVECs) and human dermal LECs (HDLECs). In mouse embryos, HoxD8 expression was significantly higher in LECs than in BECs. In a model of inflammatory lymphangiogenesis, diameters of lymphatic vessels of the diaphragm were increased by adenovirally transduced HoxD8. We also found that HoxD8 induces Ang2 expression in HDLECs and HUVECs. Moreover, we found that HoxD8 induces Prox1 expression in HUVECs and that knockdown of HoxD8 reduces this expression in HDLECs, suggesting that Prox1 expression in LECs is maintained by HoxD8. These findings indicate that transcriptional networks of Prox1 and HoxD8 play important roles in the maturation and maintenance of lymphatic vessels.

    DOI: 10.1242/jcs.052324

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  • COUP-TFII regulates the functions of Prox1 in lymphatic endothelial cells through direct interaction. 国際誌

    Tomoko Yamazaki, Yasuhiro Yoshimatsu, Yasuyuki Morishita, Kohei Miyazono, Tetsuro Watabe

    Genes to cells : devoted to molecular & cellular mechanisms   14 ( 3 )   425 - 34   2009年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    During embryonic lymphatic development, Prox1 homeobox transcription factor is expressed in a subset of venous blood vascular endothelial cells (BECs) in which COUP-TFII orphan nuclear receptor is highly expressed. Prox1 induces differentiation of BECs into lymphatic endothelial cells (LECs) by inducing the expression of various LEC markers including vascular endothelial growth factor receptor 3 (VEGFR3). However, the molecular mechanisms of how transcriptional activities of Prox1 are regulated are largely unknown. In the present study, we show that COUP-TFII plays important roles in the regulation of the function of Prox1. In BECs and LECs, Prox1 promotes the proliferation and migration toward VEGF-C by inducing the expression of cyclin E1 and VEGFR3, respectively. Gain-of-function studies showed that COUP-TFII negatively regulates the effects of Prox1 in BECs and LECs whereas loss-of-function studies showed that COUP-TFII negatively and positively regulates Prox1 in BECs and LECs, respectively. We also show that endogenous Prox1 and COUP-TFII physically interact in LECs and that both Prox1 and COUP-TFII bind to the endogenous cyclin E1 promoter. These results suggest that COUP-TFII physically and functionally interact during differentiation and maintenance of lymphatic vessels.

    DOI: 10.1111/j.1365-2443.2008.01279.x

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  • Prox1 induces lymphatic endothelial differentiation via integrin alpha 9 and other signaling cascades 査読

    Koichi Mishima, Tetsuro Watabe, Akira Saito, Yasuhiro Yoshimatsu, Natsuko Imaizumi, Shinji Masui, Masanori Hirashima, Tohru Morisada, Yuichi Oike, Makoto Araie, Hitoshi Niwa, Hajime Kubo, Toshio Suda, Kohei Miyazono

    MOLECULAR BIOLOGY OF THE CELL   18 ( 4 )   1421 - 1429   2007年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC CELL BIOLOGY  

    During embryonic lymphatic development, a homeobox transcription factor Prox1 plays important roles in sprouting and migration of a subpopulation of blood vessel endothelial cells (BECs) toward VEGF-C-expressing cells. However, effects of Prox1 on endothelial cellular behavior remain to be elucidated. Here, we show that Prox1, via induction of integrin alpha 9 expression, inhibits sheet formation and stimulates motility of endothelial cells. Prox1-expressing BECs preferentially migrated toward VEGF-C via up-regulation of the expression of integrin a9 and VEGF receptor 3 (VEGFR3). In mouse embryos, expression of VEGFR3 and integrin a9 is increased in Prox1-expressing lymphatic endothelial cells (LECs) compared with BECs. Knockdown of Prox1 expression in human LECs led to decrease in the expression of integrin a9 and VEGFR3, resulting in the decreased chemotaxes toward VEGF-C. These findings suggest that Prox1 plays important roles in conferring and maintaining the characteristics of LECs by modulating multiple signaling cascades and that integrin a9 may function as a key regulator of lymphangiogenesis acting downstream of Prox1.

    DOI: 10.1091/mbc.E06-09-0780

    Web of Science

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  • Smad7-induced beta-catenin degradation alters epidermal appendage development. 国際誌

    Gangwen Han, Allen G Li, Yao-Yun Liang, Philip Owens, Wei He, Shilong Lu, Yasuhiro Yoshimatsu, Donna Wang, Peter Ten Dijke, Xia Lin, Xiao-Jing Wang

    Developmental cell   11 ( 3 )   301 - 12   2006年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    To assess whether Smad signaling affects skin development, we generated transgenic mice in which a Smad antagonist, Smad7, was induced in keratinocytes, including epidermal stem cells. Smad7 transgene induction perturbed hair follicle morphogenesis and differentiation, but accelerated sebaceous gland morphogenesis. Further analysis revealed that independent of its role in anti-Smad signaling, Smad7 bound beta-catenin and induced beta-catenin degradation by recruiting an E3 ligase, Smurf2, to the Smad7/beta-catenin complex. Consequently, Wnt/beta-catenin signaling was suppressed in Smad7 transgenic hair follicles. Coexpression of the Smurf2 and Smad7 transgenes exacerbated Smad7-induced abnormalities in hair follicles and sebaceous glands. Conversely, when endogenous Smad7 was knocked down, keratinocytes exhibited increased beta-catenin protein and enhanced Wnt signaling. Our data reveal a mechanism for Smad7 in antagonizing Wnt/beta-catenin signaling, thereby shifting the skin differentiation program from forming hair follicles to sebaceous glands.

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  • Homeodomain interacting protein kinase 2 promotes apoptosis by downregulating the transcriptional corepressor CtBP. 国際誌

    Qinghong Zhang, Yasuhiro Yoshimatsu, Jeffrey Hildebrand, Steven M Frisch, Richard H Goodman

    Cell   115 ( 2 )   177 - 86   2003年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Genetic knockout of the transcriptional corepressor CtBP in mouse embryo fibroblasts upregulates several genes involved in apoptosis. We predicted, therefore, that a propensity toward apoptosis might be regulated through changes in cellular CtBP. To identify pathways involved in this regulation, we screened a mouse embryo cDNA library with an E1A-CtBP complex and identified the homeodomain interacting protein kinase 2 (HIPK2), which had previously been linked to UV-directed apoptosis through its ability to phosphorylate p53. Expression of HIPK2 or exposure to UV irradiation reduced CtBP levels via a proteosome-mediated pathway. The UV effect was prevented by coexpression of kinase-inactive HIPK2 or reduction in HIPK2 levels via siRNA. Mutation of the residue phosphorylated by HIPK2 prevented UV- and HIPK2-directed CtBP clearance. Finally, reduction in CtBP levels, either by genetic knockout or siRNA, promoted apoptosis in p53-deficient cells. These findings provide a pathway for UV-induced apoptosis in cells lacking p53.

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  • In vivo destabilization of dynamic microtubules by HDAC6-mediated deacetylation. 国際誌

    Akihisa Matsuyama, Tadahiro Shimazu, Yuko Sumida, Akiko Saito, Yasuhiro Yoshimatsu, Daphné Seigneurin-Berny, Hiroyuki Osada, Yasuhiko Komatsu, Norikazu Nishino, Saadi Khochbin, Sueharu Horinouchi, Minoru Yoshida

    The EMBO journal   21 ( 24 )   6820 - 31   2002年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Trichostatin A (TSA) inhibits all histone deacetylases (HDACs) of both class I and II, whereas trapoxin (TPX) cannot inhibit HDAC6, a cytoplasmic member of class II HDACs. We took advantage of this differential sensitivity of HDAC6 to TSA and TPX to identify its substrates. Using this approach, alpha-tubulin was identified as an HDAC6 substrate. HDAC6 deacetylated alpha-tubulin both in vivo and in vitro. Our investigations suggest that HDAC6 controls the stability of a dynamic pool of microtubules. Indeed, we found that highly acetylated microtubules observed after TSA treatment exhibited delayed drug-induced depolymerization and that HDAC6 overexpression prompted their induced depolymerization. Depolymerized tubulin was rapidly deacetylated in vivo, whereas tubulin acetylation occurred only after polymerization. We therefore suggest that acetylation and deacetylation are coupled to the microtubule turnover and that HDAC6 plays a key regulatory role in the stability of the dynamic microtubules.

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MISC

  • 悪性黒色腫の血管新生及び腫瘍形成能におけるIL13Rα2の役割

    高山莉那, 岡本勇人, 吉松康裕, 富澤泰志, 国田朱子, 高橋和樹, 井上カタジナアンナ, 深山正久, 福原武志, 渡部徹郎

    日本心血管内分泌代謝学会学術総会プログラム及び抄録集   23rd   2019年

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  • 悪性黒色腫の進展に伴う腫瘍血管新生におけるインターロイキン13受容体の役割

    富澤泰志, 岡本勇人, 佐藤萌希, 駒井真央, 吉松康裕, 福原武志, 原田浩徳, 渡部徹郎

    日本分子生物学会年会プログラム・要旨集(Web)   39th   2016年

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  • Etsファミリー転写因子の血管・リンパ管内皮細胞における役割

    吉松康裕, 前田健太郎, 岩田要, 宮園浩平, 渡部徹郎

    リンパ学   38 ( Supplement )   2015年

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  • 悪性黒色腫の進展に伴う腫瘍血管新生におけるIL13Rα2の役割

    富澤泰志, 岡本勇人, 駒井真央, 佐藤萌希, 吉松康裕, 福原武志, 渡部徹郎

    日本血管生物医学会学術集会プログラム・抄録集   23rd   2015年

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  • Ets-2転写因子は内皮間葉移行(EndMT)を抑制する

    前田健太郎, 吉松康裕, 福原武志, 渡部徹郎

    日本血管生物医学会学術集会プログラム・抄録集   23rd   2015年

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  • リンパ管の形成におけるTGF-βスーパーファミリーシグナルの役割 (特集 リンパ管)

    吉松 康裕, 渡部 徹郎

    生体の科学   63 ( 6 )   572 - 576   2012年11月

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    記述言語:日本語   出版者・発行元:金原一郎記念医学医療振興財団 ; 1949-  

    CiNii Article

    CiNii Books

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    その他リンク: http://search.jamas.or.jp/link/ui/2013045727

  • Prox1結合因子であるEts‐2のリンパ管新生における役割

    吉松康裕, 三平元, 森川真人, 山崎智子, 岩田要, 森下保幸, 南敬, 児玉龍彦, 宮園浩平, 渡部徹郎

    日本血管生物医学会   17th   59   2009年

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    記述言語:日本語  

    J-GLOBAL

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  • Prox1結合因子であるEts-2のリンパ管新生における役割

    吉松康裕, 三平元, 森川真人, 山崎智子, 岩田要, 森下保幸, 南敬, 児玉龍彦, 宮園浩平, 渡部徹郎

    日本血管生物医学会   17th   2009年

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受賞

  • 西賞

    2018年6月   日本リンパ学会   リンパ管内皮細胞における転写因子・シグナルネットワークの役割

    吉松 康裕

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  • 日本癌学会奨励賞

    2014年9月   日本癌学会   腫瘍脈管形成を制御する因子に関する研究

    吉松 康裕

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