New therapeutic approach to diabetic nephropathy by modulating mitochondrial function

• Project/Area Number: 18390249
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Okayama University
• Principal Investigator: MAKINO Hirofumi Okayama University, 大学院・医歯薬学総合研究科, 教授 (50165685)
• Co-Investigator(Kenkyū-buntansha): WADA Jun 岡山大学, 医学部・歯学部附属病院, 講師 (30294408) ; SHIKATA Kenichi 岡山大学, 大学院・医歯薬学総合研究科, 准教授 (00243452)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥17,180,000 (Direct Cost: ¥15,800,000、Indirect Cost: ¥1,380,000); Fiscal Year 2008: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2007: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2006: ¥11,200,000 (Direct Cost: ¥11,200,000)
• Keywords: ミトコンドリア / Tim44 / 活性酸素 / 糖尿病性腎症 / 糖尿病慢性血管合併症 / tim44

Research Abstract

生活習慣の変化により糖尿病患者は増加の一途をたどり、糖尿病性腎症により透析導入となる患者も年々増加している.糖尿病マウスへのtranslocase of inner mitochondrial membrane 44 (Tim44)遺伝子導入によって、糸球体肥大・メサンギウム基質の増加・アルブミン尿の増加が抑制された.Tim44はミトコンドリアへのsuperoxide dismutaseやglutathione dismutaseといった抗酸化酵素をimportしてミトコンドリア由来の活性酸素の産生を抑制することにより治療効果を発揮すると考えられた.

Research Products

• [Journal Article] Collectrin is involved in the development of salt-sensitive hypertension by facilitating the membrane trafficking of apical membrane proteins via interaction with soluble N-ethylmaleiamide-sensitive factor attachment protein receptor complex (2008)
  • Author(s): Yasuhara A, Wada J, Malakauskas SM, Zhang Y, Eguchi J, Nakatsuka A, Murakami K, Kanzaki M, Teshigawara S, Yamagata K, Le TH, Makino H
  • Journal Title: Circulation 118 Pages: 2146-2155
  • NAID: 130004903159
• [Journal Article] Procollagen C-proteinase enhancer-1 (PCPE-1) interacts with ・2-microglobulin (・ 2-m) and may help initiate ・2-m amyloid fibril formation in connective tissues (2008)
  • Author(s): Morimoto H, Wada J, Font B, Mott JD, Hulmes DJ, Ookoshi T, Naiki H, Yasuhara A, Nakatsuka A, Fukuoka K, Takatori Y, Ichikawa H, Akagi S, Nakao K, Makino H
  • Journal Title: Matrix Biol 27 Pages: 211-219
• [Journal Article] Increased Susceptibility to Oxidant-Mediated Tissue Injury and Peritoneal Fibrosis in Acatalasemic Mice. (2008)
  • Author(s): Fukuoka N, Sugiyama H, Inoue T, Kikumoto Y, Takiue Kl, Morinaga H, Nakao K, Maeshima Y, Asanuma M, Wang DH, Ogino K, Masuoka N, Makino H
  • Journal Title: Am J Nephrol 28 Pages: 661-668
  • Peer Reviewed
• [Journal Article] A novel variant apolipoprotein E Okayama in a patient with lipoprotein glomerulopathy (2008)
  • Author(s): Kinomura M, Sugiyama H, Saito T, Matsunaga A, Sada KE, Kanzaki M, Takazawa Y, Maeshima Y, Yanai H, Makino H
  • Journal Title: Nephrol Dial Transplant 23 Pages: 751-756
  • Peer Reviewed
• [Journal Article] Involvement of bone morphogenetic protein-4 in GH regulation byoctreotide and bromocriptine in rat pituitary GH3 cells. (2008)
  • Author(s): Miyoshi T, Otsuka F, Otani H, Inagaki K, Goto J. Yamashita M, Ogura T, Iwasaki Y, Makino H
  • Journal Title: J Endocrinol 197 Pages: 159-169
  • Peer Reviewed
• [Journal Article] Procollagen C-proteinase enhancer-1 (PCPE-1)interacts with β2-microglobulin (β2-m)and may help initiate β2-m amyloid fibril formation in connective tissues. (2008)
  • Author(s): Morimoto H, Wada J, Font B, Mott JD, Hulmes DJ, Ookoshi T, Naiki H, Yasuhara A, Nakatsuka A, Fukuoka K, Takatori Y, Ichikawa H, Akagi S, Nakao K, Makino H
  • Journal Title: Matrix Biol 27 Pages: 211-219
  • Peer Reviewed
• [Journal Article] Comparison of serum uric acid levels between Japanese with and without metabolic syndrome. (2008)
  • Author(s): Numata T, Miyatake N, Wada J, Makino H
  • Journal Title: Diabetes Res Clin Pract 80
  • Peer Reviewed
• [Journal Article] Aldosterone breakthrough caused by chronic blockage of angiotensin II type 1 receptors in human adrenocortical cells : Possible involvement of bone morphogenetic protein-6 actions. (2008)
  • Author(s): Otani H, Otsuka F, Inagaki K, Suzuki J, Miyoshi T, Kano Y, Goto J, Ogura T, Makino H
  • Journal Title: Endocrinology 149(6) Pages: 2816-2825
  • NAID: 130004903161
  • Peer Reviewed
• [Journal Article] The MUSCAT study : a Multicenter PROBE study Comparing the Effects of Angiotensin II Type-1 Receptor Blockers on Self-Monitored Home Blood Pressure in Patients with Morning Hypertension : study design and background characteristics. (2008)
  • Author(s): Uchida H, Nakamura Y, Kaihara M, Norii H, Hanayama Y, Makino H
  • Journal Title: Hypertens Res 31 Pages: 51-58
  • NAID: 10021261041
  • Peer Reviewed
• [Journal Article] Simvastatin antagonizes tumor necrosis factor-alpha inhibition of bone morphogenetic proteins-2-induced osteoblast differentiation by regulating Smad signaling and Ras/Rho-mitogen-activated protein kinase pathway. (2008)
  • Author(s): Yamashita M, Otsuka F, Mukai T, Otani H, Inagaki K, Miyoshi T, Goto J, Yamamura M, Makino H
  • Journal Title: J Endocrinol 196 Pages: 601-613
  • Peer Reviewed
• [Journal Article] Urinary excretions of lipocalin-type prostaglandin D synthase predict renal injury in type-2 diabetes : a cross-sectional and prospective multicentre study. (2008)
  • Author(s): Uehara Y, Makino H, Seiki K, Urade Y
  • Journal Title: Nephrol Dial Transplant 24(2) Pages: 475-482
  • Peer Reviewed
• [Journal Article] Chronic kidney disease perspectives in Japan and the importance of urinalysis screening・ (2008)
  • Author(s): Yamagata K, Iseki K, Nitta K, Imai H, lino Y, Matsuo s, Makino H, Hishida A
  • Journal Title: Clin Exp Nephrol 12 Pages: 1-8
  • NAID: 10025351519
  • Peer Reviewed
• [Journal Article] Collectrin is involved in the development of salt-sensitive hypertension by facilitating the membrane trafficking of apical membrane proteins via interaction with soluble N-ethylmaleiamide-sensitive factor attachment protein receptor complex. (2008)
  • Author(s): Yasuhara A, Wada J, Malakauskas SM, Zhang Y, Eguchi J, Nakatsuka A, Murakami K, Kanzaki M, Teshigawara s, Yamagata K, Le TH, Makino H
  • Journal Title: Circulation 118 Pages: 2146-2155
  • NAID: 130004903159
  • Peer Reviewed
• [Journal Article] The role for HNF-1beta-targeted collectrin in maintenance of primary cilia and cell polarity in collecting duct cells (2007)
  • Author(s): Zhang Y, Wada J, Yasuhara A, Iseda I, Eguchi J, Fukui K, Yang Q, Yamagata K, Hiesberger T, Igarashi P, Zhang H, Wang H, Akagi S, Kanwar YS, Makino H
  • Journal Title: PLoS ONE 2
• [Journal Article] Macrophage scavenger receptor-a-deficient mice are resistant against diabetic nephropathy through amelioration of microinflammation (2007)
  • Author(s): Usui HK, Shikata K, Sasaki M, Okada S, Matsuda M, Shikata Y, Ogawa D, Kido Y, Nagase R, Yozai K, Ohga S, Tone A, Wada J, Takeya M, Horiuchi S, Kodama T, Makino H
  • Journal Title: Diabetes 56 Pages: 363-372
• [Journal Article] The association of C-reactive protein with an oxidative metabolite of LDL and its implicationin atherosclerosis (2007)
  • Author(s): Tabuchi M, Inoue K, Usui-Kataoka H, Kobayashi K, Teramoto M, Takasugi K, Shikata K, Yamamura M, Ando K, Nishida K, Kasahara J, Kume N, Lopez LR, Mitsudo K, Nobuyoshi M, Yasuda T, Kita T, Makino H, Matsuura E
  • Journal Title: J Lipid Res 48 Pages: 768-781
• [Journal Article] Edaravone mimics sphingosine-1-phosphate-induced endothelial barrier enhancement in human microvascular endothelial cells (2007)
  • Author(s): Omori K, Shikata Y, Sarai K, Watanabe N, Wada J, Goda N, Kataoka N, Shikata K, Makino H
  • Journal Title: Am J Physiol Cell Physiol 293
• [Journal Article] Thiazolidinedione ameliorates renal injury in experimental diabetic rats through anti-inflammatory effects mediated by inhibition of NF-・B activation (2007)
  • Author(s): Ohga S, Shikata K, Yozai K, Okada S, Ogawa D, Usui H, Wada J, Shikata Y, Makino H
  • Journal Title: Am J Physiol Renal Physiol 292
• [Journal Article] Prevention of transition from incipient to overt nephropathy with telmisartan in patients with type 2 diabetes (2007)
  • Author(s): Makino H, Haneda M, Babazono T, Moriya T, Ito S, Iwamoto Y, Kawamori R, Takeuchi M, Katayama S
  • Journal Title: Diabetes Care 30 Pages: 1577-1578
• [Journal Article] The Role for HNF-1beta-Targeted Collectrin in Maintenance of Primary Cilia and Cell Polarity in Collecting Duct Cells. (2007)
  • Author(s): Zhang Y, Wada J, et. al.
  • Journal Title: PLoS ONE 2
  • Peer Reviewed
• [Journal Article] Changes of gene expression profiles in macrophages stimulated by angiotensin II Angiotensin II induces MCP-2 through AT1-receptor. (2007)
  • Author(s): Tone A, Shikata K, et. al.
  • Journal Title: J Renin Angiotensin Aldosterone Syst 8 Pages: 45-50
  • Peer Reviewed
• [Journal Article] Urinary PGDS levels are associated with vascular injury in type 2 diabetes patients. (2007)
  • Author(s): Yoshikawa R, wada J, et. al.
  • Journal Title: Diabetes Res Clin Pract 76 Pages: 358-367
  • Peer Reviewed
• [Journal Article] Macrophage scavenger receptor-A-deficient mice are resistant against diabetic nephropathy through amelioration of microinflammation. (2007)
  • Author(s): Usui HK, Shikata K, Sasaki M, Okada S, Matsuda M, Shikata Y, Ogawa D, Kido Y, Nagase R, Yozaki K, Ohga S, Tone A, Wada J, Takeya M, Horiuchi S, Kodama T, Makino H
  • Journal Title: Diabetes 56(2) Pages: 363-72
• [Journal Article] Therapeutic approach fodiabetic nephropathy using gene delivery of translocase of inner mitochondrial membrane 44 by reducing mitochondrial superoxide production (2006)
  • Author(s): Zhang Y, Wada J, Hashimoto I, Eguchi J, Yasuhara A, Kanwar YS, Shikata K, Makino H
  • Journal Title: J Am Soc Nephrol 17 Pages: 1090-1101
• [Journal Article] Thiazolidinediones Ameliorate Diabetic Nephropathy via Cell Cycle-Dependent Mechanisms (2006)
  • Author(s): Okada T, Wada J, Hida K, Eguchi J, Hashimoto I, Baba M, Yasuhara A, Shikata K, Makino H
  • Journal Title: Diabetes 55 Pages: 1666-1677
• [Journal Article] 2-(8-hydroxy-6-methoxy-1-oxo-1h-2-benzopyran-3-yl) propionic acid, an inhibitor of angiogenesis, ameliorates renal alterations in obese type 2 diabetic mice (2006)
  • Author(s): Ichinose K, Maeshima Y, Yamamoto Y, Kinomura M, Hirokoshi K, Kitayama H, Takazawa Y, Sugiyama H, Yamasaki Y, Agata N, Makino H
  • Journal Title: Diabetes 55 Pages: 1232-1242
• [Journal Article] Elevated serum monocyte chemoattractant protein-4 and chronic inflammation in overweight subjects (2006)
  • Author(s): Hashimoto I, Wada J, Hida A, Baba M, Miyatake N, Eguchi J, Shikata K, Makino H
  • Journal Title: Obesity (Silver Spring) 14 Pages: 799-811
• [Journal Article] Elevated serum monocyte chemoattractant protein-4 and chronic inflammation in overweight subjects. (2006)
  • Author(s): Hashimoto I, Wada J, Hida A, Baba M, Miyatake N, Eguchi J, Shikata K, Makino H
  • Journal Title: Obesity (Silver Spring) 14 Pages: 799-811
• [Journal Article] Thiazolidinediones Ameliorate Diabetic Nephropathy via Cell Cycle-Dependent Mechanisms. (2006)
  • Author(s): Okada T, Wada J, Hida K, Eguchi J, Hashimoto I, Baba M, Yasuhara A, Shikata K, Makino H
  • Journal Title: Diabetes 55 Pages: 1666-1677
• [Journal Article] Urinary PGDS levels are associated with vascular injury in type 2 diabetes patients. (2006)
  • Author(s): Yoshikawa R, Wada J, Seki K, Matsuoka T, Miyamoto S, Takahashi K, Ota S, Taniai K, Hida K, Yamakado M, Shikata K, Uehara Y, Urade Y, Makino H
  • Journal Title: Diabetes Res Clin Pract [Epub ahead of print] (In press)
• [Journal Article] Therapeutic approach for diabetic nephropathy using gene delivery of translocase of inner mitochondrial membrane 44 by reducing mitochondrial superoxide production. (2006)
  • Author(s): Zhang Y, Wada J, Hashimoto I, Eguchi J, Yasuhara A, Kanwar YS, Shikata K, Makino H
  • Journal Title: J Am Soc Nephrol 17 Pages: 1090-1101
• [Journal Article] Thiazolidinedione ameliorates renal injury in experimental diabetic rats through anti-inflammatory effects mediated by inhibition of NF-κB activation. (2006)
  • Author(s): Ohga S, Shikata K, Yozaki K, Okada S, Ogawa D, Usui H, Wada J, Shikata Y, Makino H
  • Journal Title: Am J Physiol Renal Physiol [Epub ahead of print] (in press)
• [Presentation] 会長講演動物モデルを用いた糖尿病性腎症の研究 (2009)
  • Author(s): 槇野博史
  • Organizer: 第23回日本糖尿病・肥満動物学会年次学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2009-02-13
• [Presentation] 会長講演 動物モデルを用いた糖尿病性腎症の研究 (2009)
  • Author(s): 棋野博史
  • Organizer: 第23回日本糖尿病・肥満動物学会年次学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2009-02-13
• [Presentation] CKD initiative and diabetic nephropathy in Japan (2008)
  • Author(s): Makino H
  • Organizer: The Korean Society of Nephrology Meeting
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2008-10-18
• [Presentation] CKD Initiative and Diabetic Nephropathy in Japan. (2008)
  • Author(s): Makino H
  • Organizer: The Korean Society of Nephrology Meeting
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2008-10-18
• [Presentation] The new therapeutic strategy of diabetic nephropathy based on microinflammation mechanism. The Chronic Kidney Disease in Northwest Asia (2008)
  • Author(s): Makino H
  • Organizer: The present and the Future
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2008-10-17
• [Presentation] The New Therapeutic strategy of Diabetic Nephropathy Based on Microinflammation Mechanism. (2008)
  • Author(s): Makino H
  • Organizer: The Chronic Kindney Disease in Northeast Asia : The Present and The Future
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2008-10-17
• [Presentation] Expert Investigator Award受賞講演糖尿病性腎症の発症・進展機序の解明と治療 (2008)
  • Author(s): 槇野博史
  • Organizer: 第23回日本糖尿病合併症学会
  • Place of Presentation: 東京
  • Year and Date: 2008-10-03
• [Presentation] Expert Investigator Award受賞講演 糖尿病性腎症の発症・進展機序の解明と治療 (2008)
  • Author(s): 視野博史
  • Organizer: 第23回日本糖尿病合併症学会
  • Place of Presentation: 東京
  • Year and Date: 2008-10-03
• [Presentation] CKD initiative and diabetic nephropathy in Japan (2008)
  • Author(s): Makino H
  • Organizer: Diabetic Nephropathy-CKD symposium
  • Place of Presentation: Taipei, Taiwan
  • Year and Date: 2008-07-13
• [Presentation] CKD initiative and diabetic nephropathy in Japan. (2008)
  • Author(s): Makino H
  • Organizer: Diabetic Nephropathy-CKD Symposium
  • Place of Presentation: Taipei, Taiwan
  • Year and Date: 2008-07-13
• [Presentation] 糖尿病性腎症とチーム医療 : DNETT-Japanの取り組み (2007)
  • Author(s): 槇野博史
  • Organizer: 第50回日本糖尿病学会年次学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2007-05-24
• [Presentation] 糖尿病性腎症とチーム医療:DENETT-Japanの取り組み (2007)
  • Author(s): 槇野 博史
  • Organizer: 第50回日本糖尿病学会年次学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2007-05-24