The role of senescence marker protein-30 (SMP30) in the progression of diabetic nephropathy

• Project/Area Number: 23591317
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: HASEGAWA Goji 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (00295643)
• Co-Investigator(Kenkyū-buntansha): ISHIGAMI Akihito 地方独立行政法人東京都健康長寿医療センター, 東京都健康長寿医療センター研究所, 研究副部長 (50270658) ; FUKUI Michiaki 京都府立医科大学, 医学研究科, 講師 (30247829)
• Co-Investigator(Renkei-kenkyūsha): YAMAZAKI Masahiro 京都府立医科大学, 医学研究科, 助教 (50309134)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 糖尿病 / 糖尿病腎症 / 尿細管障害 / SMP30 / 糖尿病合併症 / ビタミンC

Research Abstract

Senescence marker protein-30 (SMP30) decreases with age and contributes to the symptoms of aging. In this study, we investigated the effect of SMP30 deficiency on the pathogenesis of diabetic nephropathy using streptozocin induced diabetic SMP30 knockout (KO) mice. Tubular damages with tubulointerstitial fibrosis were observed in non-diabetic KO mice, and diabetes exacerbated these changes. On the other hand, SMP30 deletion did not affect glomerular changes. The accumulation of HIF-1alpha, the increase of oxidative stress, and tubular inflammation were associated with tubular injuries. In conclusion, decreased SMP30 with age may contribute to the progression of diabetic nephropathy through tubular damages.

Research Products

• [Journal Article] Senescence marker protein-30 / gluconolactonase deficiency exacerbates diabetic nephropathy through tubular injury in a mouse model of type 1 diabetes (2014)
  • Author(s): Okada H, Senmaru T, Fukui M, Kondo Y, Ishigami A, Maruyama N, Obayashi H, Yamazaki M, Nakamura N, Hasegawa G
  • Journal Title: J Diabetes Invest Volume: (受理、印刷中)
  • Peer Reviewed
• [Journal Article] Lepr(db/db) Mice with Senescence Marker Protein-30 Knockout (Lepr(db/db)Smp30(Y/-) ) Exhibit increases in small dense-LDL and severe fatty liver despite being fed a standard diet. (2013)
  • Author(s): Kondo Y, Hasegawa G, Okada H, Senmaru T, Fukui M, Nakamura N, Sawada M, Kitawaki J, Okanoue T, Kishimoto Y, Amano A, Maruyama N, Obayashi H, Ishigami A
  • Journal Title: PLoS One Volume: 8 Issue: 6 Pages: 65698-65698
  • DOI: 10.1371/journal.pone.0065698
  • Peer Reviewed
• [Journal Article] Pancreatic insulin release in vitamin C-deficient senescence marker protein-30/gluconolactonase knockout mice (2012)
  • Author(s): Senmaru T, Yamazaki M, Okada H, Asano M, Fukui M, Nakamura N, Obayashi H, Kondo Y, Maruyama N, Ishigami A, Hasegawa G
  • Journal Title: J Clin Biochem Nutr Volume: 50 Pages: 114-118
  • NAID: 130004466678
  • Peer Reviewed
• [Presentation] Senescence Marker Protein-30欠乏は尿細管間質線維化により糖尿病腎症進展に関与する (2013)
  • Author(s): 岡田博史、千丸貴史、石神昭人、近藤嘉高、尾林博、浅野麻衣、山崎真裕、福井道明、長谷川剛二、中村直登
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本
• [Presentation] Senescence marker protein-30 deficiency accelerates diabetic renal injury through tubulointerstitial fibrosis in a mouse model of type 1 diabetes (2013)
  • Author(s): Okada H, Senmaru T, Kondo Y, Ishigami A, Obayashi H, Asano M, Yamazaki M, Fukui M, Hasegawa G, Nakamura N
  • Organizer: 73th annual meeting and scientific sessions of American Diabetes Association
  • Place of Presentation: Chicago, USA
• [Presentation] Senescence marker protein-30 deficiency accelerates diabetic renal injury through tubulointerstitial fibrosis in a mouse model of type 1 diabetes (2013)
  • Author(s): Okada H, Senmaru T, Asano M, Yamazaki M, Fukui M, Hasegawa G, Nakamura N
  • Organizer: 49th annual meeting of the European Association for the study of Diabetes
  • Place of Presentation: Barcellona, Spain
• [Presentation] Senescence marker protein-30 deficiency accelerates diabetic renal injury through tubulointerstitial fibrosis in a mouse model of type 1 diabetes (2013)
  • Author(s): Okada H, Senmaru T, Kondo Y, Ishigami A, Obayashi H, Asano M, Yamazaki M, Fukui M, Hasegawa G, Nakamura N
  • Organizer: 73th annual meeting and scientific sessions of American Diabetes Association
  • Place of Presentation: Chicago
• [Presentation] Senescence marker protein-30 deficiency accelerates diabetic renal injury through tubulointerstitial fibrosis in a mouse model of type 1 diabetes (2013)
  • Author(s): Okada H, Senmaru T, Asano M, Yamazaki M, Fukui M, Hasegawa G, Nakamura N
  • Organizer: 49th annual meeting of the European Association for the study of Diabetes
  • Place of Presentation: Barcellona
• [Presentation] ビタミンC欠乏は糖尿病性腎症の尿細管病変の発症に関与する:SMP30 KOマウスを用いての検討 (2012)
  • Author(s): 岡田博史、千丸貴史、石神昭人、近藤嘉高、尾林博、浅野麻衣、山崎真裕、福井道明、長谷川剛二、中村直登
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: 横浜
• [Presentation] Differential effect of vitamin C deficiency on the pathogenesis of diabetic nephropathy (2012)
  • Author(s): Okada H, Senmaru T, Kondo Y, Ishigami A, Obayashi H, Asano M, Yamazaki M, Fukui M, Hasegawa G, Nakamura N
  • Organizer: 72th annual meeting and scientific sessions of American Diabetes Association
  • Place of Presentation: Philadelphia, USA
• [Presentation] ．ビタミンＣ欠乏は糖尿病性腎症の尿細管病変の発症に関与する：SMP30 KOマウスを用いての検討 (2012)
  • Author(s): 岡田博史、千丸貴史、石神昭人、近藤嘉高、尾林博、浅野麻衣、山崎真裕、福井道明、長谷川剛二、中村直登
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: 横浜
• [Presentation] Insulin Release from Pancreatic Islet in Vitamin C-Deficient Senescence Marker Protein-30/Gluconolactonase Knockout Mice (2011)
  • Author(s): Senmaru T, Hasegawa G, Ishigami A, Kondo Y, Okada H, Asano M, Yamazaki M, Fukui M, Nakamura N
  • Organizer: 71th annual meeting and scientific sessions of American Diabetes Association
  • Place of Presentation: SanDiego, USA
• [Presentation] Insulin Release from Pancreatic Islet in Vitamin C-Deficient Senescence Marker Protein-30/Gluconolactonase Knockout Mice (2011)
  • Author(s): Senmaru T, Hasegawa G, Ishigami A, Kondo Y, Okada H, Asano M, Yamazaki M, Fukui M, Nakamura N
  • Organizer: 71th annual meeting and scientific sessions of American Diabetes Association
  • Place of Presentation: SanDiego