Elucidation of the Mechanisms of Muscle-Renal Linkage and Establishment of Novel Therapeutic Strategies through Analysis of R3hdml

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16942
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Chiba University
• Principal Investigator: Ishikawa Takahiro 千葉大学, 大学院医学研究院, 特任助教 (00749426)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 筋腎連関 / 糖尿病性腎症 / サルコペニア

Outline of Final Research Achievements

This study aims to elucidate the pathogenesis of CKD and sarcopenia through the analysis of R3hdml. In mice overexpressing R3hdml, the increase in urinary protein in the diabetic state was suppressed.Expression of R3hdml increases during skeletal muscle development and differentiation in mice. Body weight and skeletal muscle mass of R3hdml knockout (KO) mice were lower compared to control mice. Expression of R3hdml increased during muscle regeneration in response to cardiotoxin (CTX)-induced muscle injury. Recovery of handgrip strength after CTX injection was significantly impaired in R3hdml KO mice, which is rescued by R3hdml.These results indicate that R3hdml is an inhibitory factor against CKD and sarcopenia.

Free Research Field

糖尿病性腎症　サルコペニア

Academic Significance and Societal Importance of the Research Achievements

今回の結果は、R3hdmlが糖尿病性腎症を始めとするCKDやサルコペニアの病態に深く関与することを示すものである。またR3hdmmlを過剰発現させることで、糖尿病性腎症やサルコペニアの状態を軽減させた。これはR3hdmlが、両者の病態において保護的な役割を果たす因子であることを示している。今後更にR3hdmlの解明することは、将来的なR3hdmlを用いた「筋腎連関」の機序解明およびCKDやサルコペニアに対する新規治療法の確立に寄与するものと期待される。