A novel VCP modulator KUS121 exerts renoprotective effects in ischemia-reperfusion injury with retaining ATP and restoring ERAD-processing capacity

Author:

Hata Yusuke1,Date Ryosuke1,Fujimoto Daisuke1,Ikeda Hanako Ohashi2,Umemoto Shuro1,Kanki Tomoko1,Nishiguchi Yoshihiko1,Mizumoto Teruhiko1,Hayata Manabu1,Kakizoe Yutaka1,Izumi Yuichiro1ORCID,Kakizuka Akira3ORCID,Mukoyama Masashi1,Kuwabara Takashige1ORCID

Affiliation:

1. Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan

2. Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan

3. Laboratory of Functional Biology, Kyoto University Graduate School of Biostudies, Kyoto, Japan

Abstract

Novel findings of this study are as follows: 1) Kyoto University substance 121 (KUS121), a novel valosin-containing protein (VCP) modulator, can reduce ATP consumption of VCP; 2) KUS121 reduced endoplasmic reticulum (ER) stress and improved cell viability in proximal tubular cells; 3) KUS121 exerted renoprotective effects against ischemia-reperfusion injury; and 4) KUS121 may prevent ischemic acute kidney injury with ATP retention and restoring ER-associated degradation capacity.

Funder

Japan Agency for Medical Research and Development

Kidney Foundation, Japan

MEXT | Japan Society for the Promotion of Science

Takeda Science Foundation

Publisher

American Physiological Society

Subject

Physiology

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