Fibroblast histone deacetylase-1 promotes kidney interstitial fibrosis following ischemia-reperfusion injury.

Interstitial fibrosis is a hallmark of chronic kidney disease, and extracellular matrix is secreted by kidney fibroblasts/pericytes that have differentiated into myofibroblasts. Class I histone deacetylases (HDACs) are highly expressed in the nucleus of kidney cells, where they regulate transcription. Class I HDAC inhibitors prevent interstitial fibrosis in preclinical models of acute kidney injury (AKI). In the warm bilateral ischemia-reperfusion injury (IRI) model, HDAC1 was the only class I HDAC with greater protein abundance following IRI, including in interstitial cells. Thus, it was hypothesized that fibroblast/myofibroblast HDAC1 activation is profibrotic.