Pharmacological inhibition of the mixed lineage leukemia 1-menin interaction aggravates acute kidney injury induced by folic acid and ischemia-reperfusion in mice

Author:

Hou Xiying1,Cui Binbin1,Qiu Andong2,Liu Na1ORCID,Zhuang Shougang13ORCID

Affiliation:

1. Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China

2. School of Life Science and Technology, Advanced Institute of Translational Medicine, Tongji University, Shanghai, China

3. Department of Medicine, Rhode Island Hospital and Alpert Medical School, Brown University, Providence, Rhode Island, United States

Abstract

Mixed lineage leukemia 1 (MLL1) is a methyltransferase that induces histone H3 lysine 4 trimethylation and exerts its functional roles by interacting with multiple subunits. In this study, we demonstrated that inhibition of MLL1 activity by MI503 or MM102 aggravated renal injury and apoptosis and suppressed renal tubular cell dedifferentiation and proliferation, suggesting that MLL1 activation during acute kidney injury acts as an intrinsic protective mechanism to mediate renal tubular cell survival and regeneration.

Funder

MOST | National Natural Science Foundation of China

Publisher

American Physiological Society

Subject

Physiology

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