Metallothionein 3: A New Player in Diabetic Nephropathy

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09372
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Asahikawa Medical College
• Principal Investigator: TAKIYAMA YUMI 旭川医科大学, 医学部, 准教授 (00396350)
• Co-Investigator(Kenkyū-buntansha): 世良 俊博 九州大学, 工学研究院, 准教授 (40373526) ; 中村 匡徳 名古屋工業大学, 工学(系)研究科(研究院), 教授 (20448046) ; 高橋 賢治 旭川医科大学, 大学病院, 医員 (00736332)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: メタロチオネイン3 / 糖尿病腎症 / HIF-1

Outline of Final Research Achievements

We hypothesized that metallothionein 3 (MT3), a novel target gene of hypoxia inducible factor-1 (HIF-1), could be involved in the diabetic glomerular injury in a retrograde fashion, via hyperglycemia-induced hypoxia in renal proximal tubules accompanied with overexpression of MT3. To clarify the role of MT3 in diabetic kidney, we generated transgenic mice, harboring a 40-kb bacterial artificial chromosome (BAC) expressing human MT3 mRNA and protein to generate humanized BAC transgenic mice (BACTGMT3). Aging-, diabetes- and high fat-induced hypoxia induced overexpression of MT3 in tubular cells in BACTGMT3 mice, resulting in narrowing the vascular lumen of peritubular capillaries by the endothelial swelling, which could retrogradely cause glomerular hypertension, leading to the glomerular injury.

Free Research Field

糖尿病、糖尿病腎症