Faculty Profiles - SAITO Akihiko

Beneficial effects of rice endosperm protein intake in Japanese men with risk factors for metabolic syndrome: a randomized, crossover clinical trial

Michihiro Hosojima, Ryohei Kaseda, Hazuki Kondo, Mikio Fujii, Masatoshi Kubota, Reiko Watanabe, Naohito Tanabe, Motoni Kadowaki, Yoshiki Suzuki, Akihiko Saito

BMC Nutrition 2 ( 1 ) 2016.5

Protective effect of composite earthworm powder against diabetic complications via increased fibrinolytic function and improvement of lipid metabolism in ZDF rats Reviewed

Tomoko Kawakami, Airi Fujikawa, Yohei Ishiyama, Michihiro Hosojima, Akihiko Saito, Masatoshi Kubota, Shinobu Fujimura, Motoni Kadowaki

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 80 ( 10 ) 1980 - 1989 2016

Language：English Publishing type：Research paper (scientific journal) Publisher：TAYLOR & FRANCIS LTD

Thrombosis is the leading cause of mortality globally. It is not only a complication but also a risk factor for progression of diabetes. However, alternative oral therapies and prophylaxis with less adverse effect for thrombosis have not been well studied. In this study, composite powder containing earthworm (CEP) was used and its fibrinolytic activity was measured. CEP was found to have a high urokinase-type plasminogen activator like activity in an in vitro assay. It also had significantly shortened euglobulin clot lysis time (ECLT) at 4 and 24h after ingestion in Sprague Dawley rats. Zucker Diabetic Fatty rats were used to assess the effect of CEP on diabetes and diabetic nephropathy. After 10weeks of feeding, CEP significantly shortened ECLT and attenuated HbA1c, hepatic lipid accumulation, and urinary albumin excretion and improved glomerular mesangial matrix score. Therefore, CEP may have beneficial effects on diabetes and diabetic nephropathy.

DOI： 10.1080/09168451.2016.1166932

Benefits of a 12-week lifestyle modification program including diet and combined aerobic and resistance exercise on albuminuria in diabetic and non-diabetic Japanese populations Reviewed

Keiko Yamamoto-Kabasawa, Michihiro Hosojima, Yusuke Yata, Mariko Saito, Noriko Tanaka, Junta Tanaka, Naohito Tanabe, Ichiei Narita, Masaaki Arakawa, Akihiko Saito

CLINICAL AND EXPERIMENTAL NEPHROLOGY 19 ( 6 ) 1079 - 1089 2015.12

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

Background Albuminuria is a biomarker for chronic kidney disease and an independent predictor of cardiovascular and all-cause mortality. A recent meta-analysis concluded that these risks increase with urinary albumin concentration, even when below the microalbuminuria threshold. Thus, minimizing urinary albumin may be a valuable therapeutic goal regardless of disease status.
Methods We investigated the benefits and safety of a 12-week lifestyle modification program including diet and combined aerobic and resistance exercise for reducing albuminuria in 295 normoalbuminuric or microalbuminuric Japanese adults, including 30 with type 2 diabetes mellitus (T2DM), 104 with metabolic syndrome (MS), and 145 with hypertension (HT).
Results In the study population, the urinary albumin:creatinine ratio (UACR) was reduced significantly (Delta UACR -3.8 +/- A 16.8 mg/g, P < 0.001) with no change in estimated glomerular filtration rate (eGFR) (Delta eGFR -0.4 +/- A 7.4 mL/min/1.73 m(2), P = 0.343). The reduction in UACR was associated with decreased fasting plasma glucose (P < 0.05). The UACR was also reduced in the T2DM, MS, and HT groups with no change in eGFR. Reduced UACR was associated with decreased fasting plasma glucose in the MS group and decreased systolic blood pressure in the HT group. The UACR was also reduced in 46 subjects using renin-angiotensin system inhibitors with no change in eGFR. Conclusions Our 12-week lifestyle modification program reduced UACR, maintained eGFR, and improved multiple fitness findings in Japanese subjects including T2DM, MS, and HT patients.

DOI： 10.1007/s10157-015-1103-5

Reduction of Albuminuria by Sitagliptin Is Associated with Improvement of Renal Proximal Tubular Function in Patients with Type 2 Diabetes Reviewed

Michihiro Hosojima, Taiji Sasagawa, Hideyuki Kabasawa, Tomomi Ishikawa, Ryohei Kaseda, Yoshiki Suzuki, Ichiei Narita, Hiroyuki Kurosawa, Yoshiaki Hirayama, Akihiko Saito

DIABETES 64 A151 - A151 2015.6

Drainage patterns of the superficial middle cerebral vein: Effects on perioperative managements of petroclival meningioma. Reviewed

Fukuda M, Saito A, Takao T, Hiraishi T, Yajima N, Fujii Y

Surgical neurology international 6 130 2015

Significance of Urinary Full-Length Megalin in Patients with IgA Nephropathy Reviewed

Takuto Seki, Katsuhiko Asanuma, Rin Asao, Kanae Nonaka, Yu Sasaki, Juan Alejandro Oliva Trejo, Hiroyuki Kurosawa, Yoshiaki Hirayama, Satoshi Horikoshi, Yasuhiko Tomino, Akihiko Saito

PLOS ONE 9 ( 12 ) e114400 2014.12

Language：English Publishing type：Research paper (scientific journal) Publisher：PUBLIC LIBRARY SCIENCE

Background and Objectives: Megalin is highly expressed at the apical membranes of proximal tubular epithelial cells. A urinary full-length megalin (C-megalin) assay is linked to the severity of diabetic nephropathy in type 2 diabetes. This study examined the relationship between levels of urinary C-megalin and histological findings in adult patients with IgA nephropathy (IgAN).
Design, Setting, Participants, & Measurements: Urine samples voided in the morning on the day of renal biopsy were obtained from 73 patients with IgAN (29 men and 44 women; mean age, 33 years) and 5 patients with membranous nephropathy (MN). Renal pathologic variables were analyzed using the Oxford classification of IgAN, the Shigematsu classification and the Clinical Guidelines of IgAN in Japan. The levels of urinary C-megalin were measured by sandwich ELISA.
Results: Histological analysis based on the Oxford classification revealed that the levels of urinary C-megalin were correlated with mesangial hypercellularity in IgAN patients (OR=1.76, 95% CI: 1.04-3.27, P<0.05). There was a significant correlation between the levels of urinary C-megalin and the severity of chronic extracapillary abnormalities according to the Shigematsu classification in IgAN patients (beta=0.33, P=0.008). The levels of urinary C-megalin were significantly higher in all risk levels of IgAN patients requiring dialysis using the Clinical Guidelines of IgAN in Japan than in the control group. The levels of urinary C-megalin were significantly higher in the high risk and very high risk grades than in the low risk grade (P<0.05). The levels of urinary C-megalin were significantly higher in MN patients compared to the control group.
Conclusions: The levels of urinary C-megalin are associated with histological abnormalities in adult IgAN patients. There is a possibility that urinary C-megalin is

DOI： 10.1371/journal.pone.0114400

The endocytic receptor megalin and its associated proteins in proximal tubule epithelial cells Reviewed

Shankhajit De, Shoji Kuwahara, Akihiko Saito

Membranes 4 ( 3 ) 333 - 335 2014.7

Language：English Publishing type：Research paper (scientific journal) Publisher：MDPI AG

Receptor-mediated endocytosis in renal proximal tubule epithelial cells (PTECs) is important for the reabsorption and metabolization of proteins and other substances, including carrier-bound vitamins and trace elements, in glomerular filtrates. Impairment of this endocytic process results in the loss of such substances and development of proteinuria, which is an important clinical indicator of kidney diseases and is also a risk marker for cardiovascular disease. Megalin, a member of the low-density lipoprotein receptor gene family, is a multiligand receptor expressed in the apical membrane of PTECs and plays a central role in the endocytic process. Megalin interacts with various intracellular adaptor proteins for intracellular trafficking and cooperatively functions with other membrane molecules, including the cubilin-amnionless complex. Evidence suggests that megalin and the cubilin-amnionless complex are involved in the uptake of toxic substances into PTECs, which leads to the development of kidney disease. Studies of megalin and its associated molecules will be useful for future development of novel strategies for the diagnosis and treatment of kidney diseases. © 2014 by the authors
licensee MDPI, Basel, Switzerland.

DOI： 10.3390/membranes4030333

RELATIONSHIP BETWEEN LEVELS OF URINARY FULL-LENGTH MEGALIN AND HISTOLOGICAL FINDINGS IN PATIENTS WITH IgA NEPHROPATHY Reviewed

Seki Takuto, Asanuma Katsuhiko, Asao Rin, Nonaka Kanae, Kodama Fumiko, Sasaki Yu, Akiba-Takagi Miyuki, Hosoe-Nagai Yoshiko, Kurosawa Hiroyuki, Hirayama Yoshiaki, Horikoshi Satoshi, Saito Akihiko, Tomino Yasuhiko

NEPHROLOGY 19 146 - 146 2014.5

Keap1 inhibition attenuates glomerulosclerosis Reviewed

Yoichi Miyazaki, Akihiro Shimizu, Ira Pastan, Keiko Taguchi, Eriko Naganuma, Takafumi Suzuki, Tatsuo Hosoya, Takashi Yokoo, Akihiko Saito, Toshio Miyata, Masayuki Yamamoto, Taiji Matsusaka

NEPHROLOGY DIALYSIS TRANSPLANTATION 29 ( 4 ) 783 - 791 2014.4

Language：English Publishing type：Research paper (scientific journal) Publisher：OXFORD UNIV PRESS

NFE2-related factor 2 (Nrf2) is a master regulatory transcription factor for antioxidant genes. Inhibition of its adaptor protein, Kelch-like ECH-associated protein 1 (Keap1), activates Nrf2. Podocyte injury triggers the progressive deterioration of glomerular damage toward glomerulosclerosis. We examined whether modulation of the Keap1-Nrf2 system has an impact on this process.
Methods. Nrf2 null-mutant (KO) and Keap1 hypomorphic knockdown (KD) mice were crossed with NEP25 mice, in which podocyte-specific injury can be induced by an immunotoxin.
Results. Thiobarbituric acid reactive substances, 8-hydroxy-deoxyguanosine and phosphorylated JNK were increased in the injured NEP25 kidney. Real-time PCR revealed that Keap1 KD upregulated Nrf2 target genes, including Gclc, Gclm, Gstp1, Gstp2 and Nqo1 in the glomerulus. However, podocyte injury did not upregulate these genes in Keap1 wild-type mice, nor did it further increase the expression of those genes in Keap1 KD mice. Three weeks after the induction of podocyte injury, glomerulosclerosis was considerably more attenuated in Keap1 KD mice than in control mice (median sclerosis index, 0.27 versus 3.03, on a 0-4 scale). Keap1 KD mice also showed considerably preserved nephrin staining (median index, 6.76 versus 0.91, on a 0-8 scale) and decreased glomeruli containing desmin-positive injured podocytes (median percentage, 24.5% versus 85.8%), along with a decrease in mRNAs for Fn1, Tgfb1, Col4a4 and Col1a2.
Conclusions. Thus, podocyte injury cannot effectively activate Nrf2, but Nrf2 activation by Keap1 knockdown attenuates glomerulosclerosis. These results indicate that the Nrf2-Keap1 system is a promising drug target for the treatment of chronic kidney diseases.

DOI： 10.1093/ndt/gfu002

Upregulation of prolactin receptor in proximal tubular cells was induced in cardiac dysfunction model mice Reviewed

Yohei Tsuchida, Yoshikatsu Kaneko, Tadashi Otsuka, Kei Goto, Akihiko Saito, Keiko Yamamoto, Tadashi Yamamoto, Ichiei Narita

CLINICAL AND EXPERIMENTAL NEPHROLOGY 18 ( 1 ) 65 - 74 2014.2

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

In order to clarify the interaction between cardiac dysfunction and sodium homeostasis in the kidney, we used a murine model of cardiac dysfunction and investigated the effect on sodium transporters in renal tubular cells.
Cardiac function was deteriorated by abdominal aortic banding, and the gene expression of sodium transporters in the kidneys was evaluated by real-time RT-PCR and compared with that in the kidneys of control mice.
Gene expression of all three variants of the murine prolactin receptor was enhanced by aortic banding. Upregulated prolactin receptor was distributed in the proximal tubular cells of the pars recta in the deep inner cortex and the outer stripe of the outer medulla. Prolactin has been reported to be a natriuretic hormone that inhibits proximal tubular Na+/K+-ATPase activity, resulting in reduced sodium reabsorption and the acceleration of natriuresis. Inhibition of endogenous prolactin secretion by bromocriptine administration decreased the urine sodium excretion in both aortic banding and control mice. On the other hand, excess exogenous prolactin administration enhanced urine potassium excretion in aortic banding mice. Furthermore, a high-sodium diet accelerated urinary sodium excretion, which was also significantly decreased by inhibition of endogenous prolactin secretion in aortic banding mice.
We reported that the prolactin receptor was upregulated by aortic banding treatment. Prolactin-prolactin receptor interaction in the proximal tubular cells of the pars recta should involve a different mechanism of kaliuresis other than inhibition of Na+/K+-ATPase.

DOI： 10.1007/s10157-013-0820-x

Erratum to: Decreased urinary calbindin 1 levels in proteinuric rats and humans with distal nephron segment injuries (Clinical and Experimental Nephrology DOI: 10.1007/s10157-013-0835-3) Reviewed

Tomoko Iida, Hidehiko Fujinaka, Bo Xu, Ying Zhang, Sameh Magdeldin, Masaaki Nameta, Zan Liu, Yutaka Yoshida, Eishin Yaoita, Shuichi Tomizawa, Akihiko Saito, Tadashi Yamamoto

Clinical and Experimental Nephrology 18 ( 3 ) 444 2014

Decreased urinary calbindin 1 levels in proteinuric rats and humans with distal nephron segment injuries Reviewed

Tomoko Iida, Hidehiko Fujinaka, Bo Xu, Ying Zhang, Sameh Magdeldin, Masaaki Nameta, Zan Liu, Yutaka Yoshida, Eishin Yaoita, Shuichi Tomizawa, Akihiko Saito, Tadashi Yamamoto

Clinical and Experimental Nephrology 18 ( 3 ) 432 - 443 2014

Language：English Publishing type：Research paper (scientific journal) Publisher：Springer-Verlag Tokyo

Background: Several proteins have been proposed as new urinary biomarkers of kidney injuries, but they are not always capable of identifying the kidney nephron segment that has been injured. Since calbindin 1 protein is exclusively localized in the kidney distal nephron segment, it is presumed that its expression is altered during distal nephron segment injuries, resulting in changes in its urinary excretion. Methods: Calbindin 1 expression in normal rat kidneys was compared with that in the kidneys of rats that had suffered distal nephron segment injuries (unilateral ureteral obstruction [UUO] or anti-glomerular basement membrane glomerulonephritis [anti-GBM GN]) using immunohistochemical examinations and real-time polymerase chain reaction. The urinary calbindin 1 protein concentration of normal rats was also compared with that of anti-GBM GN rats and of cisplatin nephropathy rats using Western blotting. We also compared the kidney and urinary calbindin 1 protein concentrations of normal human subjects with those of proteinuric patients [immunoglobulin (Ig)A nephropathy
IgAN] with distal nephron segment injuries. Results: Calbindin 1 mRNA expression in the renal cortices and calbindin 1 protein expression in the kidney distal nephron segments were decreased in the UUO and anti-GBM GN rat kidneys. The urinary calbindin 1 protein levels of the anti-GBM GN rats were also markedly decreased, whereas those of the cisplatin nephropathy rats were slightly decreased. The human IgAN patients displayed decreased renal calbindin 1 protein expression in their dilated distal tubules, and some patients displayed decreased urinary calbindin 1 levels. Conclusion: Since it has been demonstrated that decreased urinary calbindin 1 levels are indicative of decreased calbindin 1 kidney expression due to distal nephron segment injuries, calbindin 1 might be a useful urinary biomarker for identifying distal nephron segment injuries. © 2013 Japanese Society of Nephrology.

DOI： 10.1007/s10157-013-0835-3

Successful removal of a huge hypervascular tentorial cavernous angioma after preoperative endovascular embolization: Case report Reviewed

Junichi Yoshimura, Yoshihiro Tsukamoto, Masakazu Sano, Hitoshi Hasegawa, Kazuhiko Nishino, Akihiko Saito, Masafumi Fukuda, Kouichirou Okamoto, Yukihiko Fujii

Journal of Neurosurgery: Pediatrics 14 ( 1 ) 43 - 47 2014

Language：English Publishing type：Research paper (scientific journal) Publisher：American Association of Neurological Surgeons

The authors report a rare case of a huge hypervascular tentorial cavernous angioma treated with preoperative endovascular embolization, followed by successful gross-total removal. A 15-year-old girl presented with scintillation, diplopia, and papilledema. Computed tomography and MRI studies revealed a huge irregularly shaped tumor located in the right occipital and suboccipital regions. The tumor, which had both intra- and extradural components, showed marked enhancement and invasion of the overlying occipital bone. Angiography revealed marked tumor stain, with blood supply mainly from a large branch of the left posterior meningeal artery. Therefore, this lesion was diagnosed as a tentorium-based extraaxial tumor. For differential diagnosis, meningioma, hemangiopericytoma, and malignant skull tumor were considered. Tumor feeders were endovascularly embolized with particles of polyvinyl alcohol. On the following day, the tumor was safely gross totally removed with minimum blood loss. Histopathological examination confirmed the diagnosis of cavernous angioma. To date, there have been no reports of tentorium-based cavernous angiomas endovascularly embolized preoperatively. A tentorial cavernous angioma is most likely to show massive intraoperative bleeding. Therefore, preoperative embolization appears to be quite useful for safe maximum resection. Hence, the authors assert that the differential diagnosis of tentorium-based tumors should include tentorial cavernous angioma, for which preoperative endovascular embolization should be considered. ©AANS, 2014.

DOI： 10.3171/2014.4.PEDS13628

Rice protein ameliorates the progression of diabetic nephropathy in Goto-Kakizaki rats with high-sucrose feeding Reviewed

Masatoshi Kubota, Reiko Watanabe, Hideyuki Kabasawa, Noriaki Iino, Akihiko Saito, Takehisa Kumagai, Shinobu Fujimura, Motoni Kadowaki

BRITISH JOURNAL OF NUTRITION 110 ( 7 ) 1211 - 1219 2013.10

Language：English Publishing type：Research paper (scientific journal) Publisher：CAMBRIDGE UNIV PRESS

The effect of rice protein (RP) on diabetic nephropathy in non-obese, spontaneous type 2 diabetic Goto-Kakizaki (GK) rats was investigated. GK rats at 7 weeks of age were fed 20% RP or casein (C) in standard or high-sucrose diets for 10 weeks. Plasma total cholesterol, TAG, alkaline phosphatase (ALP), adiponectin, creatinine and urinary albumin excretion (UAE) were measured and renal histology was evaluated. Compared with C, RP lowered plasma TAG and improved plasma adiponectin levels in GK rats fed the standard diet (P<0.05), and also lowered total cholesterol and ALP in high-sucrose-fed GK rats (P<0.05). RP markedly suppressed the sharp increase in UAE when GK rats were fed high-sucrose diets (P<0.05), and prevented glomerular mesangial matrix expansion in the deep renal cortex near the corticomedullary junction (P<0.05). These results strongly indicate that dietary RP can ameliorate the progression of diabetic nephropathy at an early stage compared with C.

DOI： 10.1017/S0007114513000354

Rice Protein Ameliorates Progression of Diabetic Nephropathy in Goto-Kakizaki Rats with High-Sucrose Feeding Reviewed

Kubota M, Watanabe R, Kabasawa H, Iino N, Saito A, Kumagai T, Fujimura S, Kadowaki M

British Journal of Nutrition 110 ( 7 ) 1211 - 1219 2013.7

GFR ESTIMATION BY URINARY SOLUBLE MEGALIN

Akira Hiwatashi, Masahiro Hagiwara, Syuichi Tsuruoka, Joichi Usui, Kei Nagai, Hirayasu Kai, Naoki Morito, Chie Saito, Keigyo Yoh, Michihiro Hosojima, Akihiko Saito, Kunihiro Yamagata

NEPHROLOGY DIALYSIS TRANSPLANTATION 28 ( 1 ) 145 - 145 2013.5

Dietary alkali-extracted rice protein improves some diabetes-related markers in obese type 2 diabetic rats Reviewed

Watanabe Reiko, Kubota Masatoshi, Yamaguchi Miki, Saito Akihiko, Fujii Mikio, Fujimura Shinobu, Kadowaki Motoni

FASEB JOURNAL 27 2013.4

Protective effects of alkali-extracted rice protein on diabetic nephropathy in obese type 2 diabetic rats Reviewed

Masatoshi Kubota, Reiko Watanabe, Miki Yamaguchi, Michihiro Hosojima, Akihiko Saito, Mikio Fujii, Shinobu Fujimura, Motoni Kadowaki

FASEB JOURNAL 27 2013.4

Intraoperative monitoring of motor evoked potentials during glioma removal Reviewed

Masafumi Fukuda, Makoto Oishi, Tetsuro Takao, Tetsuya Hiraishi, Tsutomu Kobayashi, Hiroshi Aoki, Ryosuke Ogura, Akihiko Saito, Yukihiko Fujii

Neurological Surgery 41 ( 3 ) 219 - 227 2013.3

Language：Japanese Publishing type：Research paper (scientific journal)

Objective : To determine whether motor evoked potentials (MEPs) provide reliable monitoring of the motor system during resection of gliomas in or adjacent to the motor cortex or pyramidal tract. Materials and methods : MEP recording was performed during 64 operations in 55 patients harboring gliomas. Intraoperative MEP findings were classified into 3 groups : Group A was defined as having no significant MEP changes, Group B as having reversible MEP changes (≥50% amplitude decrease or loss), and Group C as having irreversible changes. Postoperative motor function was evaluated according to the presence/absence of deterioration immediately after surgery and 1 month later, as compared to preoperative motor status Results : Immediately after surgery, 13 of 39 (33%) patients in Group A, 6 of 17 (35%) in Group B, and 7 of 8 (88%) in Group C experienced deterioration of motor function. One month after surgery, 4 of 39 (10%) patients in Group A, 3 of 17 (18%) in Group B, and 4 of 8 (50%) showed deterioration of motor function Both immediately (χ2=8.3, p&lt
0.05) and 1 month (χ2=6.9. p&lt
0.05) after surgery, MEP alterations correlated significantly with postoperative deterioration of motor function. Despite MEPs being stable throughout surgery (Group A), there were some patients with deterioration of motor function initially appearing to represent false negative monitoring. However, these deteriorations were confirmed to have been caused by secondary hemorrhage, venous return dysfunction, postoperative convulsion, or resection of the supplementary motor area. Conclusions : MEP monitoring provides reliable information on the motor system during glioma surgery. Although false negative MEP results may exist in some patients, most data were not influenced by intraoperative manipulation but rather were attributable to secondary postoperative events.