Loss of p300 in proximal tubular cells reduces renal fibrosis and endothelial-mesenchymal transition.

ABSTRACT: Chronic kidney disease (CKD) has a high prevalence worldwide and is typically accompanied by severe fibrosis. However, the exact pathogenesis of renal fibrosis and effective treatments have yet to be identified. In this study, we found that expression of the histone-acetyltransferase p300 was increased in focal segmental glomerulosclerosis patients and several distinct mouse models of renal fibrosis. Moreover, we showed that the AKT-mediated phosphorylation of Ser-1834 of p300 increased the stability of p300 upon renal fibrosis induction, and conversely, PPM1K specifically dephosphorylated p300 at Ser-1834, resulting in a significant reduction in p300 stability and renal fibrosis. Interestingly, increased p300 in proximal tubular cells (PTCs) promoted renal fibrosis development by mediatin

SUBMITTER: Kim H 

PROVIDER: S-EPMC12254316 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature