The role of matrix metalloproteinase-2 in kidney fibrosis

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17738
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Mie University
• Principal Investigator: Nishihama Kota 三重大学, 医学部附属病院, 助教 (90832527)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 腎線維化 / 糖尿病腎症 / マトリックスメタロプロテイナーゼ2 / アポトーシス

Outline of Final Research Achievements

In our in vivo experiment using transgenic mice overexpressing human MMP2, it took longer than expected to induce renal fibrosis in the control group of mice. In addition, new insights related MMP2 and renal disorder were reported from other research insutitutes. Due to these factors, we were unable to complete the analysis of the direct effects of MMP-2 on renal fibrosis within the period.
On the other hand, the relationship between TGFβ1, which is a related substance of MMP2, and renal fibrosis could be shown by experiments using glomerular-specific human transforming growth factor-β1 transgenic mice. In addition, we were able to show that the anti-apoptotic effect of thrombomodulin suppresses the progression of renal fibrosis.
We also found that peptides from certain bacteria influence the progression of TGFβ1-mediated organ fibrosis.

Free Research Field

糖尿病・内分泌内科

Academic Significance and Societal Importance of the Research Achievements

本研究で、MMP2に関連した物質が腎線維化を進行させる詳細な機序を解明し、その抑制方法についても明らかにすることができた。また、特定の細菌が産生する物質が臓器の線維化に関与する可能性についても明らかにすることができた。これらの研究結果は、糖尿病腎症をはじめとする慢性腎疾患の早期発見や進行抑制方法を確立するために役立つものと考える。