TGF-β1 promotes expression of fibrosis-related genes through the induction of histone variant H3.3 and histone chaperone HIRA.

ABSTRACT: Renal fibrosis is a histological manifestation that occurs in almost every type of chronic kidney disease. Histone variant H3.3 and its chaperone, histone cell cycle regulation defective homolog A (HIRA), serve as epigenetic marks that regulate transcriptional activity. In this study, we assessed the roles of histone H3.3 and HIRA in unilateral ureteral-obstruction (UUO) mice. In UUO mice, the levels of histone H3.3 and HIRA were significantly upregulated in the kidneys. These upregulated levels were decreased by a TGF-β1 neutralizing antibody. TGF-β1 induced histone H3.3 and HIRA expression in vitro via a Smad3-dependent pathway in normal rat kidney (NRK)-52E cells. Additionally, knockdown of HIRA expression decreased histone H3.3 expression and fibrogenesis in NRK-52E cells after TGF-β1

SUBMITTER: Shindo T 

PROVIDER: S-EPMC6145928 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature