Tubular- glomerular interaction nd metabolic kidney disease

2016 Fiscal Year Final Research Report

• Project/Area Number: 26253053
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Keio University
• Principal Investigator: Itoh Hiroshi 慶應義塾大学, 医学部(信濃町), 教授 (40252457)
• Co-Investigator(Kenkyū-buntansha): 長谷川 一宏 慶應義塾大学, 医学部, 助教 (30424162) ; 脇野 修 慶應義塾大学, 医学部, 准教授 (50265823)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 慢性腎臓病 / 糖尿病性腎症 / 肥満関連腎症 / 近位尿細管 / 糸球体

Outline of Final Research Achievements

We defined chronic kidney disease based on the diabetes, obesity, and hypertension as metabolic kidney disease and found the molecular mechanism. We delineated the pathological relevance of iNAMPT of proximal tubular cells. The expression of iNAMPT was reduced by TGFb in diabetic kidney disease. We also analyzed regulatory mechanism for the promoter activity of iNMPT genes. In diabetic kidney disease, iNAMPT expression was downregulated which contributed to the tissue fibrotic changes through the reduced expressions of Sirt6. We also investigated the role of NMMT in the pathogenesis of tissue fibrotic changes of both kidney and liver. NMMT-overexpressing mice exhibited prominent liver fibrosis but not renal fibrosis. Liver fibrosis was demonstrated to result from the decreased turnover of methionine metabolism, which lead to methyl-donor deficiency and epigenetic induction of CTGF gene in the liver.

Free Research Field

内分泌学、腎臓病学