The role of metallothionein in diabetic nephropathy

• Project/Area Number: 25461223
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Okayama University
• Principal Investigator: Ogawa Daisuke 岡山大学, 医歯(薬)学総合研究科, 准教授 (70535195)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 糖尿病性腎症 / 酸化ストレス / 炎症

Outline of Final Research Achievements

Metallothionein (MT) is induced in proximal tubular epithelial cells as an antioxidant in diabetic kidney; however, the role of MT in renal function remains unclear. We therefore investigated if MT deficiency accelerates diabetic nephropathy through oxidative stress and inflammation. Diabetes was induced by streptozotocin injection in MT-deficient (MT-/-) and MT+/+ mice. Murine proximal tubular epithelial cells were used to elucidate the role of MT under high-glucose conditions. Parameters of diabetic nephropathy and markers of ROS and inflammation were accelerated in diabetic MT-/- mice compared with diabetic MT+/+ mice. In vitro studies demonstrated that knockdown of MT by small interfering RNA enhanced mitochondrial ROS generation and inflammation-related gene expression in cultured cells under high-glucose conditions. These results suggest that MT may play a key role in protecting the kidney against high glucose-induced ROS and subsequent inflammation in diabetic nephropathy.

Research Products

• [Journal Article] Identification of Circulating miR-101, miR-375 and miR-802 as Biomarkers for Type 2 Diabetes. (2015)
  • Author(s): Higuchi C, Nakatsuka A, Eguchi J, Teshigawara S, Kanzaki M, Katayama A, Yamaguchi S, Takahashi N, Murakami K, Ogawa D, Sasaki S, Makino H, Wada J.
  • Journal Title: Metabolism Volume: 64(4) Issue: 4 Pages: 489-97
  • DOI: 10.1016/j.metabol.2014.12.003
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Translocase of inner mitochondrial membrane 44 alters the mitochondrial fusion and fission dynamics and protects from type 2 diabetes. (2015)
  • Author(s): Wang Y, Katayama A, Terami T, Han X, Nunoue T, Zhang D, Teshigawara S, Eguchi J, Nakatsuka A, Murakami K, Ogawa D, Furuta Y, Makino H, Wada J.
  • Journal Title: Metabolism Volume: 未定 Issue: 6 Pages: 677-88
  • DOI: 10.1016/j.metabol.2015.02.004
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Nuclear hormone receptor expression in mouse kidney and renal cell lines (2014)
  • Author(s): Ogawa D, Eguchi J, Wada J, Terami N, Hatanaka T, Tachibana H, Nakatsuka A, Horiguchi CS, Nishii N, Makino H
  • Journal Title: PLoS ONE Volume: 9(1) Issue: 1 Pages: e85594-e85594
  • DOI: 10.1371/journal.pone.0085594
  • NAID: 120005723280
  • Peer Reviewed
• [Journal Article] Pemt deficiency ameliorates endoplasmic reticulum stress in diabetic nephropathy (2014)
  • Author(s): Watanabe M, Nakatsuka A, Murakami K, Inoue K, Terami T, Higuchi C, Katayama A, Teshigawara S, Eguchi J, Ogawa D, Watanabe E, Wada J, Makino H
  • Journal Title: PLoS ONE Volume: 9(3) Issue: 3 Pages: e92647-e92647
  • DOI: 10.1371/journal.pone.0092647
  • NAID: 120005723281
  • Peer Reviewed
• [Journal Article] Long-term treatment with the sodium glucose cotransporter 2 inhibitor, dapagliflozin, ameliorates glucose homeostasis and diabetic dephropathy in db/db mice. (2014)
  • Author(s): Terami N, Ogawa D, Tachibana H, Hatanaka T, Wada J, Nakatsuka A, Eguchi J, Horiguchi CS, Nishii N, Yamada H, Takei K, Makino H.
  • Journal Title: PLoS One Volume: 9 Issue: 6 Pages: e100777-e100777
  • DOI: 10.1371/journal.pone.0100777
  • Peer Reviewed / Open Access
• [Journal Article] Metallothionein deficiency exacerbates diabetic nephropathy in streptozotocin-induced diabetic mice (2014)
  • Author(s): Tachibana H, Ogawa D, Sogawa N, Asanuma M, Miyazaki I, Terami N, Hatanaka T, Horigushi CS, Nakatsuka A, Eguchi J, Wada J, Yamada H, Takei K, Makino H
  • Journal Title: Am J Physiol Renal Physiol Volume: 306 Issue: 1 Pages: 105-115
  • DOI: 10.1152/ajprenal.00034.2013
  • Peer Reviewed / Open Access
• [Journal Article] Urinary fetuin-A is a novel marker for diabetic neohropathy in type 2 diabetes identified by lectin microarray (2013)
  • Author(s): Inoue K, Wada J, Eguchi J, Nakatsuka A, Teshigawara S, Murakami K, Ogawa D, Terami T, Katayama A, Tone A, Iseda I, Hida K, Yamada M, Ogawa T, Makino H
  • Journal Title: PLoS ONE Volume: 8(10) Issue: 10 Pages: e77118-e77118
  • DOI: 10.1371/journal.pone.0077118
  • Peer Reviewed
• [Presentation] 抗酸化蛋白メタロチオネインと糖尿病性腎症
  • Author(s): 小川大輔
  • Organizer: 第43回日本腎臓学会西部学術大会
  • Place of Presentation: 松山市