Demethylation of H3K9 and H3K27 Contributes to the Tubular Renal Damage Triggered by Endoplasmic Reticulum Stress.

ABSTRACT: Loss of protein homeostasis (proteostasis) in the endoplasmic reticulum (ER) activates the unfolded protein response (UPR), restoring correct protein folding. Sustained ER stress exacerbates activation of the major UPR branches (IRE1α/XBP1, PERK/ATF4, ATF6), inducing expression of numerous genes involved in inflammation, cell death, autophagy, and oxidative stress. We investigated whether epigenetic dynamics mediated by histone H3K9 and H3K27 methylation might help to reduce or inhibit the exacerbated and maladaptive UPR triggered in tubular epithelial cells. Epigenetic treatments, specific silencing, and chromatin immunoprecipitation assays were performed in human proximal tubular cells subjected to ER stress. Pharmacological blockage of KDM4C and JMJD3 histone demethylases with SD-70 and

SUBMITTER: Diaz-Bulnes P 

PROVIDER: S-EPMC9312208 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature