研究者業績

淺沼 克彦

アサヌマ カツヒコ  (Katsuhiko Asanuma)

基本情報

所属
千葉大学  大学院医学研究院腎臓内科学 教授
学位
医学博士(順天堂大学)

J-GLOBAL ID
200901026502687112
researchmap会員ID
1000264166

外部リンク

学歴

 2

論文

 144
  • Yuji Ishibashi, Takanori Matsui, Keisuke Ohta, Ryuichiro Tanoue, Masayoshi Takeuchi, Katsuhiko Asanuma, Kei Fukami, Seiya Okuda, Kei-ichiro Nakamura, Sho-ichi Yamagishi
    Microvascular Research 87 100 2013年  査読有り
  • Ishibashi Y, Matsui T, Ohta K, Tanoue R, Takeuchi M, Asanuma K, Fukami K, Okuda S, Nakamura K, Yamagishi S
    Microvascular research 85 54-58 2013年1月  査読有り
  • Yuji Ishibashi, Takanori Matsui, Keisuke Ohta, Ryuichiro Tanoue, Masayoshi Takeuchi, Katsuhiko Asanuma, Kei Fukami, Seiya Okuda, Kei-ichiro Nakamura, Sho-ichi Yamagishi
    Microvascular Research 85(1) 54-58 2013年1月  査読有り
    Advanced glycation end products (AGEs) formed at an accelerated rate under diabetes, elicit oxidative and pro-apoptotic reactions in various types of cells, including podocytes, thus being involved in the development and progression of diabetic nephropathy. Recently, we, along with others, have found that pigment epithelium-derived factor (PEDF), a glycoprotein with potent neuronal differentiating activity, inhibits AGE-elicited mesangial and tubular cell damage through its anti-oxidative properties. However, the effects of PEDF on podocyte loss, one of the characteristic features of diabetic nephropathy remain unknown. In this study, we investigated whether and how PEDF could protect against AGE-elicited podocyte apoptosis in vitro. AGEs decreased PEDF mRNA level in podocytes, which was blocked by neutralizing antibody raised against receptor for AGEs (RAGE-Ab). PEDF or RAGE-Ab was found to inhibit the AGE-induced up-regulation of RAGE mRNA level, oxidative stress generation and resultant apoptosis in podocytes. All of the beneficial effects of PEDF on AGE-exposed podocytes were blocked by the treatment of GW9662, an inhibitor of peroxisome proliferator-activated receptor-γ (PPARγ). Further, although PEDF did not affect protein expression levels of PPARγ, it significantly restored the PPARγ transcriptional activity in AGE-exposed podocytes. The present results demonstrated for the first time that PEDF could block the AGE-induced apoptotic cell death of podocytes by suppressing RAGE expression and subsequent ROS generation partly via PPARγ activation. Our present study suggests that substitution of PEDF proteins may be a promising strategy for preventing the podocyte loss in diabetic nephropathy. © 2012 Elsevier Inc.
  • Kodama F, Asanuma K, Takagi M, Hidaka T, Asanuma E, Fukuda H, Seki T, Takeda Y, Hosoe-Nagai Y, Asao R, Horikoshi S, Tomino Y
    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 2012年11月  査読有り
  • Asao R, Asanuma K, Kodama F, Akiba-Takagi M, Nagai-Hosoe Y, Seki T, Takeda Y, Ohsawa I, Mano S, Matsuoka K, Kurosawa H, Ogasawara S, Hirayama Y, Sekine S, Horikoshi S, Hara M, Tomino Y
    Clinical journal of the American Society of Nephrology : CJASN 7 1385-1393 2012年9月  査読有り
  • Asao R, Asanuma K, Kodama F, Akiba-Takagi M, Nagai-Hosoe Y, Seki T, Takeda Y, Ohsawa I, Mano S, Matsuoka K, Kurosawa H, Ogasawara S, Hirayama Y, Sekine S, Horikoshi S, Hara M, Tomino Y
    Clinical journal of the American Society of Nephrology : CJASN 7(9) 1385-1393 2012年9月1日  査読有り
    Owner : NLM<br /> Status : MEDLINE<br /> PubModel : Print-Electronic<br /> Language : eng<br /> Pagination : 1385-93
  • Nakata J, Ohsawa I, Onda K, Tanimoto M, Kusaba G, Takeda Y, Kobayashi N, Asanuma K, Tanaka Y, Sato M, Inami Y, Suzuki H, Suzuki H, Masuda A, Nonaka K, Sasaki Y, Hisada A, Hamada C, Horikoshi S, Tomino Y
    Journal of clinical laboratory analysis 26 248-253 2012年7月  査読有り
  • Junichiro Nakata, Isao Ohsawa, Kisara Onda, Mitsuo Tanimoto, Gaku Kusaba, Yukihiko Takeda, Noriyoshi Kobayashi, Katsuhiko Asanuma, Yuichi Tanaka, Michiko Sato, Yuko Inami, Hitoshi Suzuki, Hiyori Suzuki, Atsumi Masuda, Kanae Nonaka, Yu Sasaki, Atsuko Hisada, Chieko Hamada, Satoshi Horikoshi, Yasuhiko Tomino
    Journal of Clinical Laboratory Analysis 26(4) 248-253 2012年7月  査読有り
    Background: Accurate estimation of the glomerular filtration rate (GFR) is very important in clinical practice. Although renal inulin clearance (Cin) is the gold standard for measuring GFR, the procedure for Cin measurement is complicated. Use of GFR-estimating equations has been increasing recently due to their simplicity. The objectives of the present study are to analyze the correlation between Cin and other GFR-estimating parameters and to investigate their clinical usefulness and limitation. Methods: Seventy-two Japanese patients were enrolled in this study. Cin was measured by the continuous infusion method. Serum creatinine (s-Cr), cystatin C, uric acid (UA), and hemoglobin (Hb) were measured. The Japanese formula of estimated GFR (eGFR) was as follows: eGFR (ml/min/1.73m2) = 194 × s-Cr-1.094 × Age-0.287 × 0.739 (if female). The endogenous creatinine clearance test was also performed. Results: Levels of Cin were highly correlated with those of endogenous creatinine clearance (Ccr) (R2 = 0.7585) and eGFR (R2 = 0.5659). However, patients with lower Cin showed unexpectedly elevated levels of endogenous Ccr and eGFR. Moreover, the levels of eGFR tended to be unexpectedly increased in patients with low body surface area. Conclusion: Although GFR-estimating equations are useful for estimating GFR accurately, they pose a risk of overestimation of kidney function in patients with decreased GFRor a poor physique. © 2012 Wiley Periodicals, Inc.
  • 淺沼 克彦, 日高 輝夫, 富野 康日己
    日本内科学会雑誌 101(4) 1092-1101 2012年4月10日  
    臨床の現場では,原因疾患を問わず腎障害の重要なマーカーとして蛋白尿が使用されている.正常人では高度な蛋白尿は認められないが,何らかの原因により血液の濾過装置である糸球体が障害を受けると,糸球体構成細胞の一つである糸球体足細胞(ポドサイト)が障害を受け,著明な蛋白尿が生じる.ポドサイトは高度に分化した細胞であり,糸球体内皮細胞と糸球体基底膜を外側から覆い,血中蛋白質の最終的な濾過障壁としての機能を果たしている.ポドサイト障害の早期には,まずスリット膜の分子構造の変化と足突起の細胞骨格であるアクチン骨格の分布が変化し,足突起は消失してその噛み合わせを失う.ポドサイト障害が長く持続すると糸球体基底膜上からポドサイトは脱落し,糸球体硬化・慢性腎不全へと進行して行く.最近,ポドサイト障害から糸球体硬化にいたるメカニズムが,分子生物学的手法を用い急速に解明されつつあり,ポドサイトのアクチン骨格再構成・細胞死・オートファジーなどが関係することがわかってきた.ポドサイトにおけるこれらの機序の解明とともに,ポドサイトにターゲットを絞った新規治療薬が検索されつつある.<br>
  • Asanuma K, Hidaka T, Tomino Y
    Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine 101(4) 1092-101 2012年4月  
  • Takagi-Akiba Miyuki, Asanuma Katsuhiko, Tanida Isei, Tada Norihiro, Trejo Juan Alejandro Oliva, Nonaka Kanae, Asanuma Etsuko, Kominami Eiki, Ueno Takashi, Tomino Yasuhiko
    AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY 302(3) F380-F389 2012年2月  査読有り
  • Miyuki Takagi-Akiba, Katsuhiko Asanuma, Isei Tanida, Norihiro Tada, Juan Alejandro Oliva Trejo, Kanae Nonaka, Etsuko Asanuma, Eiki Kominami, Takashi Ueno, Yasuhiko Tomino
    American Journal of Physiology - Renal Physiology 302(3) F380-F389 2012年2月  査読有り
    Autophagy is a process of cellular degradation, and its dysfunction elicits many pathological symptoms. However, the contribution of autophagy to kidney glomerular function has not been fully clarified. We previously reported that LC3, a promising executor of autophagy, played an important role in recovery from podocyte damage in an experimental nephrosis model (Asanuma K, Tanida I, Shirato I, Ueno T, Takahara H, Nishitani T, Kominami E, Tomino Y. FASEB J 17: 1165-1167, 2003). γ-Aminobutyric acid A receptor-associated protein (GABARAP), has recently been characterized as another homolog of LC3, although its precise role in autophagy remains unclear. We recently generated green fluorescent protein (GFP)-GABARAP transgenic mice, in which GFP-GABARAP is abundantly expressed in glomerular podocytes. We found that the transgenic mice showed no obvious phenotype, and podocytes isolated from these mice manifested autophagic activity almost equivalent to that of wild-type mice when measured in vitro. Surprisingly, a single injection of doxorubicin caused a greater increase in proteinuria and sclerotic glomeruli in transgenic mice compared with wild-type mice. Under these conditions, neither GFP-GABARAP nor endogenous GABARAP appeared to be recruited to autophagosomes, and both remained in the cytosol. Moreover, the cytosolic GFP-GABARAP was significantly colocalized with p62 to form aggregates. These results indicate that the GFP-GABARAP/p62 complex is responsible for impairment of glomerular function and that it retards recovery from the effects of doxorubicin. © 2012 the American Physiological Society.
  • Yuji Ishikawa, Takamichi Ito, Mitsuo Tanimoto, Shinji Hagiwara, Masako Furukawa, Saori Yamaguchi, Keisuke Omote, Katsuhiko Asanuma, Tomohito Gohda, Yoshio Shimizu, Kazuhiko Funabiki, Satoshi Horikoshi, Yasuhiko Tomino
    Journal of Diabetes Mellitus 02(03) 346-352 2012年  
  • Lydia A, Asanuma K, Nonaka K, Takagi M, Jeong KH, Kodama F, Asao R, Asanuma E, Prodjosudjadi W, Tomino Y
    American journal of nephrology 35 58-68 2012年  査読有り
  • Lei B, Nakano D, Fujisawa Y, Liu Y, Hitomi H, Kobori H, Mori H, Masaki T, Asanuma K, Tomino Y, Nishiyama A
    Journal of pharmacological sciences 119(4) 359-367 2012年  査読有り
  • Bai Lei, Daisuke Nakano, Yoshihide Fujisawa, Ya Liu, Hirofumi Hitomi, Hiroyuki Kobori, Hirohito Mori, Tsutomu Masaki, Katsuhiko Asanuma, Yasuhiko Tomino, Akira Nishiyama
    Journal of pharmacological sciences 119(4) 359-67 2012年  査読有り
    We recently demonstrated that cilnidipine, an L/N-type calcium channel blocker, elicits protective effects against glomerular podocyte injury, in particular, in obese hypertensive rats that express the N-type calcium channel (N-CC). Since the N-CC is known to be expressed in sympathetic nerve endings, we evaluated the reno-protective effects of cilnidipine in innervated and denervated spontaneously hypertensive rats (SHR). Male SHR were uninephrectomized and fed 4% high-salt diet (HS-UNX-SHR). Animals were divided into groups, as follows, and observed from 9 to 27 weeks of age: 1) vehicle (n = 14), 2) vehicle plus renal-denervation (n = 15), 3) cilnidipine (50 mg/kg per day, p.o.; n = 10), and 4) cilnidipine plus renal-denervation (n = 15). Renal denervation attenuated elevations in blood pressure, but failed to suppress urinary protein excretion and podocyte injury in HS-UNX-SHR. Cilnidipine in both innervated and denervated HS-UNX-SHR similarly induced significant antihypertensive effects, as well as suppressing the urinary protein excretion and podocyte injury, compared to vehicle-treated HS-UNX-SHR. These data indicate that renal nerves have a limited contribution to the cilnidipine-induced reno-protective effects in HS-UNX-SHR.
  • Aida Lydia, Katsuhiko Asanuma, Kanae Nonaka, Miyuki Takagi, Kyung-Hwan Jeong, Fumiko Kodama, Rin Asao, Etsuko Asanuma, Wiguno Prodjosudjadi, Yasuhiko Tomino
    American Journal of Nephrology 35(1) 58-68 2012年1月  査読有り
    Background: In various animal studies, vitamin D has been shown to have a significant effect on reduction of proteinuria and the progression of kidney disease. However, little is known on its renoprotective effect in adriamycin (ADR)-induced nephrosis mice. The present study was intended to determine the therapeutic benefit of 22-oxa-calcitriol (OCT), a vitamin D analog, in reducing proteinuria and its renoprotective effect, i.e. preventing podocyte injury on ADR-induced nephrosis mice. Methods: Three experimental groups were used as follows: (1) nephrosis mice, established by a single intravenous injection of ADR (2) ADR+OCT mice, nephrosis mice treated with OCT, and (3) mice treated only with OCT as the control group. Podocyte injury was assessed by podocyte apoptosis using the TUNEL assay, podocyte counting, podocyte-specific expressed protein by immunofluorescence and Western blot analysis, and foot process effacement using electron microscopy. Results: Lower proteinuria was observed in ADR+OCT mice. Improvement in glomerulosclerosis and interstitial fibrosis, and prevention of glomerular hyperfiltration were observed in ADR+OCT mice. Immunofluorescence and Western blot analyses showed restoration of downregulated expression of nephrin, CD2AP and podocin. Nevertheless, dendrin expression was not restored. An insignificant reduction in podocyte numbers was found in ADR+OCT mice. Complete foot process effacement was partially prevented in ADR+OCT mice. Conclusions: The results indicate that OCT reduces podocyte injury and has renoprotective effects in ADR nephrosis mice. Copyright © 2011 S. Karger AG, Basel.
  • Yasuhiko Tomino, Yoshio Shimizu, Chieko Hamada, Atsushi Kurusu, Isao Ohsawa, Yusuke Suzuki, Toshinao Tsuge, Hiroaki Io, Noriyoshi Kobayashi, Yukihiko Takeda, Katsuhiko Asanuma, Yuichi Tanaka, Hitoshi Suzuki, Jun-ichiro Nakata, Katsuhiko Takara, Satoshi Horikoshi
    JOURNAL OF NEPHROLOGY 24(6) 756-763 2011年11月  査読有り
    Background: The long-term antiproteinuric effects of benidipine, a calcium channel blocker (CCB), have not been evaluated in detail in hypertensive patients with chronic kidney disease (CKD). Methods: Benidipine (4 mg/day) was administered to previously untreated hypertensive patients with CKD, or hypertensive patients with CKD not achieving target blood pressure (BP) despite taking an angiotensin II receptor blocker (ARB). The patients were followed up for 1 year. If target BP was not achieved by 2 weeks after the start of benidipine treatment, the dosage was increased to 8 mg/day. The urinary protein to creatinine (UP/cre) ratio was evaluated before and after benidipine treatment. Results: This study evaluated 65 hypertensive patients with CKD. BP (systolic/diastolic) decreased from 154 +/- 19 / 91 +/- 12 mm Hg before treatment to 134 +/- 16 / 78 +/- 10 mm Hg at 1 year after treatment (p&lt;0.001). The UP/cre ratio decreased significantly from 2.21 +/- 2.47 g/g creatinine (g/g cre) before treatment to 1.43 +/- 2.21 g/g cre after treatment (p&lt;0.001). In both the untreated and ARB-treated groups, the BP and UP/cre ratio decreased significantly at 1 year after treatment. The percentage change in the UP/cre ratio was signifi-cantly greater in patients aged 65 years or older than in those less than 65 years (79.1% vs. 48.7%, p=0.038). Conclusions: Benidipine treatment reduced the UP/cre ratio in hypertensive patients with CKD, and the percentage decrease of the UP/cre ratio was greater in elderly patients, suggesting that benidipine may have more potent antiproteinuric effects in elderly hypertensive patients with CKD.
  • Ito N, Nishibori Y, Ito Y, Takagi H, Akimoto Y, Kudo A, Asanuma K, Sai Y, Miyamoto K, Takenaka H, Yan K
    Laboratory investigation; a journal of technical methods and pathology 91(11) 1584-1595 2011年11月  査読有り
  • Noriko Ito, Yukino Nishibori, Yugo Ito, Hisashi Takagi, Yoshihiro Akimoto, Akihiko Kudo, Katsuhiko Asanuma, Yoshimichi Sai, Ken-Ichi Miyamoto, Hitoshi Takenaka, Kunimasa Yan
    Laboratory Investigation 91(11) 1584-1595 2011年11月  査読有り
    Although podocyte damage is known to be responsible for the development of minimal-change disease (MCD), the underlying mechanism remains to be elucidated. Previously, using a rat MCD model, we showed that endoplasmic reticulum (ER) stress in the podocytes was associated with the heavy proteinuric state and another group reported that a mammalian target of rapamycin complex 1 (mTORC1) inhibitor protected against proteinuria. In this study, which utilized a rat MCD model, a combination of immunohistochemistry, dual immunofluorescence and confocal microscopy, western blot analysis, and quantitative real-time RT-PCR revealed co-activation of the unfolded protein response (UPR), which was induced by ER stress, and mTORC1 in glomerular podocytes before the onset of proteinuria and downregulation of nephrin at the post-translational level at the onset of proteinuria. Podocyte culture experiments revealed that mTORC1 activation preceded the UPR that was associated with a marked decrease in the energy charge. The mTORC1 inhibitor everolimus completely inhibited proteinuria through a reduction in both mTORC1 and UPR activity and preserved nephrin expression in the glomerular podocytes. In conclusion, mTORC1 activation may perturb the regulatory system of energy metabolism primarily by promoting energy consumption and inducing the UPR, which underlie proteinuria in MCD. © 2007 USCAP, Inc All rights reserved.
  • Katsuhiko Asanuma, Miyuki Akiba-Takagi, Fumiko Kodama, Rin Asao, Yoshiko Nagai, Aida Lydia, Hiromitsu Fukuda, Eriko Tanaka, Terumi Shibata, Hisatsugu Takahara, Teruo Hidaka, Etsuko Asanuma, Eiki Kominami, Takashi Ueno, Yasuhiko Tomino
    American Journal of Nephrology 33(6) 537-549 2011年6月  査読有り
    Background: Adriamycin (ADR) nephrosis in mice has been extensively studied and has enabled a greater understanding of the processes underlying the progression of renal injury. Dendrin is a novel component of the slit diaphragm with proapoptotic signaling properties, and it accumulates in the podocyte nucleus in response to glomerular injury in mice. The present study re-evaluated chronic progressive nephropathy in ADR mice and the localization of dendrin in mice and in human glomerulopathy. Methods: To investigate the localization of dendrin, a mouse model of nephrosis and glomerulosclerosis was used, in which ADR was injected once. WT-1-positive cells and apoptotic cells were counted in vivo and in vitro. To check the expression of dendrin in ADR mice, immunostaining and Western blot were performed. A survey of dendrin staining was performed on human kidney biopsy specimens. Results: The injection of ADR induced proteinuria, podocyte loss and glomerulosclerosis. It also caused the relocation of dendrin from the slit diaphragm to the podocyte nucleus. We demonstrated the location of dendrin to podocyte nuclei in several cases of human glomerulopathy. The mean occurrence of dendrin-positive nucleus per glomerulus increased in several cases of human glomerulopathy. Conclusions: These findings suggest that the relocation of dendrin to the podocyte nuclei is useful as a novel marker of podocyte injury in human glomerulopathy. Copyright © 2011 S. Karger AG, Basel.
  • Katsuhiko Asanuma, Miyuki Akiba-Takagi, Fumiko Kodama, Rin Asao, Yoshiko Nagai, Aida Lydia, Hiromitsu Fukuda, Eriko Tanaka, Terumi Shibata, Hisatsugu Takahara, Teruo Hidaka, Etsuko Asanuma, Eiki Kominami, Takashi Ueno, Yasuhiko Tomino
    AMERICAN JOURNAL OF NEPHROLOGY 33(6) 537-549 2011年  査読有り
    Background: Adriamycin (ADR) nephrosis in mice has been extensively studied and has enabled a greater understanding of the processes underlying the progression of renal injury. Dendrin is a novel component of the slit diaphragm with proapoptotic signaling properties, and it accumulates in the podocyte nucleus in response to glomerular injury in mice. The present study re-evaluated chronic progressive nephropathy in ADR mice and the localization of dendrin in mice and in human glomerulopathy. Methods: To investigate the localization of dendrin, a mouse model of nephrosis and glomerulosclerosis was used, in which ADR was injected once. WT-1-positive cells and apoptotic cells were counted in vivo and in vitro. To check the expression of dendrin in ADR mice, immunostaining and Western blot were performed. A survey of dendrin staining was performed on human kidney biopsy specimens. Results: The injection of ADR induced proteinuria, podocyte loss and glomerulosclerosis. It also caused the relocation of dendrin from the slit diaphragm to the podocyte nucleus. We demonstrated the location of dendrin to podocyte nuclei in several cases of human glomerulopathy. The mean occurrence of dendrin-positive nucleus per glomerulus increased in several cases of human glomerulopathy. Conclusions: These findings suggest that the relocation of dendrin to the podocyte nuclei is useful as a novel marker of podocyte injury in human glomerulopathy. Copyright (C) 2011 S. Karger AG, Basel
  • Yasuhiko Tomino, Katsuhiko Asanuma, Hiroaki Io, Hitoshi Suzuki, Yuichi Tanaka, Junichiro Nakata, Noriyoshi Kobayashi, Yukihiko Takeda, Yuko Inami, Yoshio Shimizu, Toshinao Tsuge, Yusuke Suzuki, Isao Ohsawa, Atsushi Kurusu, Chieko Hamada, Satoshi Horikoshi, Michiro Wakabayashi, Tatsuya Aoki, Yasuhiko Kaneguchi, Ichiyu Sho
    Therapeutic Research 31(10) 1471-1480 2010年10月20日  
    Objective : Objective of the present study is to evaluate the stable potency of PS-Ca Jelly in CKD patients with hyperkalemia. Materials and Methods : We examined 55 hyperkalemic patients (serum potassium concentration &gt 5.0 mEq/L) caused by CKD. Jelly type formulation of PS-Ca (PS-Ca 5 g/25 g Jelly=one cup) was used in this study. One to three cups which contained 5-15 g PS-Ca were administered depending on the patients' condition for more than 6 months. Serum potassium level, electrolytes and indexes of renal function were measured every two months during the study period. Results : Serum creatinine, SUN, proteinurea, blood pressure and HbA1c in these patients did not change and patients' clinical conditions were stable during this study period. Serum potassium levels were 5.56±0.05 mEq/L at baseline, 4.69±0.05 mEq/L after two months, 4.79±0.06 mEq/L after 4 months, 4.72±0.06 mEq/L after 6 months, 4.76±0.07 mEq/L after 8 months and 4.79±0.09 mEq/L after 10 months, respectively. Serum potassium reduction after the treatment (average observation period : 8.36±0.24 months) was 0.82±0.06 mEq/L. Different daily dose of PS-Ca Jelly reduced serum potassium level in a dose dependent manner [one cup/day : 0.65±0.05 mEq/L (p&lt 0.001), two cups/day : 0.84±0.15 mEq/L (p&lt 0.001), three cups/day : 1.00±0.11 mEq/L (p&lt 0.001)]. Conclusion : It appears that PS-Ca Jelly was effective for the treatment of hyperkalemia in CKD patients and its potency was stable during 10 months study period. This effect also showed a dose dependence.
  • Fan YY, Kohno M, Nakano D, Ohsaki H, Kobori H, Suwarni D, Ohashi N, Hitomi H, Asanuma K, Noma T, Tomino Y, Fujita T, Nishiyama A
    Journal of hypertension 28 1034-1043 2010年5月  査読有り
  • Yu-Yan Fan, Masakazu Kohno, Daisuke Nakano, Hiroyuki Ohsaki, Hiroyuki Kobori, Diah Suwarni, Naro Ohashi, Hirofumi Hitomi, Katsuhiko Asanuma, Takahisa Noma, Yasuhiko Tomino, Toshiro Fujita, Akira Nishiyama
    Journal of hypertension 28(5) 1034-43 2010年5月  査読有り
    OBJECTIVES: Clinical studies have indicated the beneficial effect of an L/N-type calcium channel blocker (CCB), cilnidipine, on the progression of proteinuria in hypertensive patients compared with an L-type CCB, amlodipine. In the present study, we examined the effects of cilnidipine and amlodipine on the renal injury in spontaneously hypertensive rat/ND mcr-cp (SHR/ND) and their underlying mechanism. METHODS AND RESULTS: SHR/ND were treated with vehicle (nU10), cilnidipine [33 mg/kg per day, orally (p.o.); nU11] or amlodipine (20 mg/kg per day, p.o.; nU9) for 20 weeks. SHR/ND developed proteinuria in an age-dependent manner. Cilnidipine suppressed the proteinuria greater than amlodipine did. The immunohistochemical analysis showed that N-type calcium channel and Wilm's tumor factor, a marker of podocyte, were co-expressed. SHR/ND had significantly greater desmin staining, an indicator of podocyte injury, with lower podocin and nephrin expression in the glomeruli than Wistar-Kyoto rat or SHR. Cilnidipine significantly prevented the increase in desmin staining and restored the glomerular podocin and nephrin expression compared with amlodipine. Cilnidipine also prevented the increase in renal angiotensin II content, the expression and membrane translocation of NADPH oxidase subunits and dihydroethidium staining in SHR/ND. In contrast, amlodipine failed to change these renal parameters. CONCLUSION: These data suggest that cilnidipine suppressed the development of proteinuria greater than amlodipine possibly through inhibiting N-type calcium channel-dependent podocyte injury in SHR/ND.
  • 高木 美幸, 淺沼 克彦, 児玉 史子, 浅尾 りん, 高原 久嗣, 多田 昇弘, 富野 康日己
    順天堂医学 55(3) 367-367 2009年9月  
  • 高木 美幸, 浅沼 克彦, 谷田 以誠, 児玉 史子, 浅尾 りん, 高原 久嗣, 多田 昇弘, 小松 雅明, 上野 隆, 木南 英紀, 富野 康日己
    順天堂医学 55(3) 377-377 2009年9月  
  • Sekine Y, Nishibori Y, Akimoto Y, Kudo A, Ito N, Fukuhara D, Kurayama R, Higashihara E, Babu E, Kanai Y, Asanuma K, Nagata M, Majumdar A, Tryggvason K, Yan K
    Journal of the American Society of Nephrology : JASN 20(7) 1586-1596 2009年7月  査読有り
  • Yuji Sekine, Yukino Nishibori, Yoshihiro Akimoto, Akihiko Kudo, Noriko Ito, Daisuke Fukuhara, Ryota Kurayama, Eiji Higashihara, Ellappan Babu, Yoshikatsu Kanai, Katsuhiko Asanuma, Michio Nagata, Årindam Majumdar, Karl Tryggvason, Kunimasa Yan
    Journal of the American Society of Nephrology 20(7) 1586-1596 2009年7月  査読有り
    LAT3 is a Na+-independent neutral L-amino acid transporter recently isolated from a human hepatocellular carcinoma cell line. Although liver, skeletal muscle, and pancreas are known to express LAT3, the tissue distribution and physiologic function of this transporter are not completely understood. Here, we observed that glomeruli express LAT3. Immunofluorescence, confocal microscopy, and immunoelectron microscopy revealed that LAT3 localizes to the apical plasma membrane of podocyte foot processes. In mice, starvation upregulated glomerular LAT3, phosphorylated AKT1, reconstituted the actin network, and elongated foot processes. In the fetal kidney, we observed intense LAT3 expression at the capillary loops stage of renal development. Finally, zebrafish morphants lacking lat3 function showed collapsed glomeruli with thickened glomerular basement membranes. Permeability studies of the glomerular filtration barrier in these zebrafish morphants demonstrated a disruption of selective glomerular permeability. Our data suggest that LAT3 may play a crucial role in the development and maintenance of podocyte structure and function by regulating protein synthesis and the actin cytoskeleton. Copyright © 2009 by the American Society of Nephrology.
  • 高原 久嗣, 白土 公, 淺沼 克彦, 坂本 慶子, 堀越 哲, 富野 康日己
    日本腎臓学会誌 51(3) 259-259 2009年4月  
  • 高木 美幸, 淺沼 克彦, 谷田 以誠, 児玉 史子, 浅尾 りん, 高原 久嗣, 多田 昇弘, 小松 雅明, 上野 隆, 木南 英紀, 富野 康日己
    日本腎臓学会誌 51(3) 318-318 2009年4月  
  • Asanuma K, Tomino Y
    Nihon Jinzo Gakkai shi 50(5) 532-9 2008年1月  
  • K Asanuma, K Kim, J Oh, L Giardino, S Chabanis, C Faul, J Reiser, P Mundel
    JOURNAL OF CLINICAL INVESTIGATION 115(5) 1188-1198 2005年5月  査読有り
    Synaptopodin is the founding member of a novel class of proline-rich actin-associated proteins highly expressed in telencephalic dendrites and renal podocytes. Synaptopodin-deficient (synpo(-/-)) mice lack the dendritic spine apparatus and display impaired activity-dependent long-term synaptic plasticity. In contrast, the ultrastructure of podocytes in synpo(-/-) mice is normal. Here we show that synpo(-/-) mice display impaired recovery from protamine sulfate-induced podocyte foot process (FP) effacement and LPS-induced nephrotic syndrome. Similarly, synpo(-/-) podocytes show impaired actin filament reformation in vitro. We further demonstrate that synaptopodin exists in 3 isoforms, neuronal Synpo-short (685 AA), renal Synpo-long (903 AA), and Synpo-T (181 AA). The C terminus of Synpo-long is identical to that of Synpo-T. All 3 isoforms specifically interact with a-actinin and elongate alpha-actinin-induced actin filaments. synpo(-/-) mice lack Synpo-short and Synpo-long expression but show an upregulation of Synpo-T protein expression in podocytes, though not in the brain. Gene silencing of Synpo-T abrogates stress-fiber formation in synpo(-/-) podocytes, demonstrating that Synpo-T serves as a backup for Synpo-long in synpo(-/-) podocytes. In concert, synaptopodin regulates the actin-bundling activity of a-actinin in highly dynamic cell compartments, such as podocyte FPs and the dendritic spine apparatus.
  • J Reiser, G von Gersdorff, M Loos, J Oh, K Asanuma, L Giardino, MP Rastaldi, N Calvaresi, H Watanabe, K Schwarz, C Faul, M Kretzler, A Davidson, H Sugimoto, R Kalluri, AH Sharpe, JA Kreidberg, P Mundel
    JOURNAL OF CLINICAL INVESTIGATION 113(10) 1390-1397 2004年5月  査読有り
    Kidney podocytes and their slit diaphragms form the final barrier to urinary protein loss. This explains why podocyte injury is typically associated with nephrotic syndrome. The present study uncovered an unanticipated novel role for costimulatory molecule B7-1 in podocytes as an inducible modifier of glomerular permselectivity. B7-1 in podocytes was found in genetic, drug-induced, immune-mediated, and bacterial toxin-induced experimental kidney diseases with nephrotic syndrome. The clinical significance of our results is underscored by the observation that podocyte expression of B7-1 correlated with the severity of human lupus nephritis. In vivo, exposure to low-dose LPS rapidly upregulates B7-1 in podocytes of WT and SCID mice, leading to nephrotic-range proteinuria. Mice lacking B7-1 are protected from LPS-induced nephrotic syndrome, suggesting a link between podocyte B7-1 expression and proteinuria. LPS signaling through toll-like receptor-4 reorganized the podocyte actin cytoskeleton in vitro, and activation of B7-1 in cultured podocytes led to reorganization of vital slit diaphragm proteins. In summary, upregulation of B7-1 in podocytes may contribute to the pathogenesis of proteinuria by disrupting the glomerular filter and provides a novel molecular target to tackle proteinuric kidney diseases. Our findings suggest a novel function for B7-1 in danger signaling by nonimmune cells.
  • Asanuma K, Tanida I, Shirato I, Ueno T, Takahara H, Nishitani T, Kominami E, Tomino Y
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology 17(9) 1165-7 2003年6月  査読有り
  • 高原 久嗣, 白土 公, 浅沼 克彦, 武田 之彦, 富野 康日己
    順天堂医学 49(1) 109-109 2003年5月  
  • 山下 倫史, 堀越 哲, 浅沼 克彦, 高原 久嗣, 武田 之彦, 白土 公, 富野 康日己
    日本腎臓学会誌 45(3) 303-303 2003年4月  
  • 高原 久嗣, 白土 公, 浅沼 克彦, 武田 之彦, 富野 康日己
    日本腎臓学会誌 44(3) 235-235 2002年4月  
  • 浅沼 克彦, 白土 公, 谷田 以誠, 高原 久嗣, 西谷 寛仁, 上野 隆, 木南 英紀, 富野 康日己
    日本腎臓学会誌 44(3) 236-236 2002年4月  
  • 浅沼 克彦, 白土 公, 高原 久嗣, 富野 康日己, 谷田 以誠, 上野 隆, 木南 英紀
    順天堂医学 47(4) 534-534 2002年3月  
  • Asanuma K, Yokoyama K, Tsukada T, Takemoto F, Hara S, Yamada A, Tomino Y
    Nephron 88(1) 39-43 2001年5月  査読有り
  • Shirato, I, K Asanuma, Y Takeda, K Hayashi, Y Tomino
    JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 11(12) 2381-2386 2000年12月  査読有り
    Parietal epithelial cells (PEC) of Bowman's capsules cover the inner aspect of Bowman's capsules and are believed to contribute to extracapillary lesions of glomerulonephritis such as crescent formation. In glomerular research including cell culture experiments and pathology, differentiation between PEC and podocytes has frequently been a major problem. Immunohistochemistry of the adult rat kidney for protein gene product 9.5 (PGP 9.5), a neuron-specific ubiquitin C-terminal hydrolase, demonstrated selective localization of the immunoreactivity in PEG. At the urinary pole of the glomerulus, immunoreactive PEC were clearly differentiated from proximal tubular cells that were negative for PGP 9.5. In the subcapsular nephrogenic zone of newborn rat kidney, immunoreactivity was observed in almost all cells in the comma-shaped body and early S-shaped body and selectively in PEC in the late S-shaped body and capillary-stage glomerulus. In rat glomerular disease models (Masugi-nephritis and puromycin aminonucleoside nephrosis), cells that consisted of cellular crescents or adhered to glomerular tufts were positive for PGP 9.5. The selective localization of PGP 9.5 in PEC in rat kidney provides a new cytochemical marker for identifying the cells. Developmental expression of the protein suggests that PGP 9.5 is involved in the processes of nephrogenesis of rat kidney.
  • Takao Okada, Katsuhiko Asanuma, Tai Nakamura, Rikuo Ochi
    Pathophysiology 6(1) 27-33 1999年4月  査読有り
    Hydrogen peroxide (H2O2) contributes to the development of reperfusion injury. The aim of this study was to characterize the effects of H2O2 on cardiac function, autacoid release and myocardial damage. Rat hearts were Langendorff-perfused with Krebs solution containing 70, 200 or 700 μM H2O2 for 30 min, then washed out with normal Krebs solution. The left ventricular pressure, heart rate and coronary perfusion pressure were monitored, released prostanoid and NO was quantified and the activity of released glutamic oxaloacetic transaminase (GOT) was estimated. H2O2 (70 μM) significantly increased prostacyclin release with no evidence of myocardial damage. H2O2 (200 μM) stimulated the release of all the prostanoids quantified markedly without affecting NO release. GOT release did not increase during H2O2 perfusion, but did increase after washout. Inhibition of prostanoid release with indomethacin did not affect the washout-induced increase in GOT release. These results indicate that a low concentration of H2O2 stimulates prostanoid release without affecting myocardial contraction, while higher concentrations damage the heart indirectly. The mechanism of the washout- induced myocardial damage is not clear yet, but the H2O2-induced change in prostanoid release did not seem to be responsible for the damage.
  • Tomino Y, Shimizu Y, Hamada C, Kurusu A, Ohsawa I, Suzuki Y, Tsuge T, Io H, Kobayashi N, Takeda Y, Asanuma K, Tanaka Y, Suzuki H, Nakata J, Takara K, Horikoshi S
    Journal of nephrology 24(6) 756-63  査読有り

MISC

 72

講演・口頭発表等

 10

担当経験のある科目(授業)

 1

共同研究・競争的資金等の研究課題

 18