The hypoxia-inducible factor-α prolyl hydroxylase inhibitor FG4592 ameliorates renal fibrosis by inducing the H3K9 demethylase JMJD1A

Author:

Ike Takeshi1,Doi Shigehiro1ORCID,Nakashima Ayumu12,Sasaki Kensuke1ORCID,Ishiuchi Naoki1,Asano Tomoichiro3,Masaki Takao1ORCID

Affiliation:

1. Department of Nephrology, Hiroshima University Hospital, Hiroshima, Japan

2. Department of Stem Cell Biology and Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

3. Department of Medical Science, Graduate School of Medicine, Hiroshima University, Hiroshima, Japan

Abstract

Using a mouse model of renal fibrosis and transforming growth factor-β1-stimulated rat cell lines, we show that treatment with FG4592, an inhibitor of hypoxia-inducible factor-1α and -2α (HIF-1α/2α) prolyl hydroxylase decreases renal fibrosis and concomitantly reduces methylated lysine 9 of histone H3 (H3K9) levels via upregulation of Jumonji domain-containing 1a (JMJD1A). The results identify a novel role for the HIF-1α/2α-JMJD1A-H3K9 regulatory axis in suppressing renal fibrosis.

Funder

MEXT | Japan Society for the Promotion of Science

Publisher

American Physiological Society

Subject

Physiology

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