The protective role of heme oxygenase-1 and autophagy in the kidney rhabdomyolysis-associated acute kidney injury

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K10980
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Okayama University
• Principal Investigator: Shimizu Hiroko 岡山大学, 医学部, 客員研究員 (80423284)
• Co-Investigator(Kenkyū-buntansha): 井上 一由 岡山大学, 医学部, 客員研究員 (10624413) ; 森松 博史 岡山大学, 医歯薬学総合研究科, 教授 (30379797) ; 高橋 徹 岡山県立大学, 保健福祉学部, 教授 (40252952)
• Research Collaborator: YAMAOKA Masakazu ; OMORI Emiko
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 集中治療学 / 急性腎不全 / 横紋筋融解症 / ヘムオキシゲナーゼー１ / Bach1 / オートファジー

Outline of Final Research Achievements

We demonstrate that nuclear Bach1 protein was rapidly and significantly decreased in the kidneys of rats with glycerol-associated RM-AKI, followed by an increase in Bach1 protein in the cytosol, which was preceded by the induction of Bach1 mRNA. We detected a significant increase in HO-1 expression and the robust inhibition of ALAS1 expression in the kidneys of glycerol-treated animals, suggesting a significant increase in the free
heme concentration in the kidney of glycerol-treated animals. Bach1 is a heme responsive transcription repressor of the HO-1 gene, and our findings suggest that changes in the subcellular distribution of Bach1 may be involved in the induction of HO-1 accompanying heme metabolism in the kidney of the rat RM-AKI model. To the best of our knowledge, this is the first study to show dynamic changes in renal Bach1 expression in vivo, which were associated with heme metabolism.

Free Research Field

医歯薬学