Mechanism of renal fibrosis
Chronic kidney disease (CKD) is typically associated with severe fibrosis, the exact pathogenesis of which remains unclear.
The researchers show that histone acetyltransferase p300 was upregulated in CKD patient kidneys and mouse renal fibrosis models.
Knocking down proximal tubule-specific p300 in mouse renal fibrosis models alleviated kidney fibrosis.
They also demonstrate that the protein stability of p300 in proximal tubular cells was regulated by the phosphatase PPM1K and proximal tubular p300 induced endothelial-mesenchymal transition in adjacent endothelial cells and promotes fibrosis.
A p300-specific inhibitor treatment mitigated kidney fibrosis in mouse renal fibrosis models.
https://www.embopress.org/doi/full/10.1038/s44321-025-00243-1
