Chromatin dynamics at the core of kidney fibrosis

Abstract

Progression of chronic kidney disease is a principal challenge in Nephrology, as effective therapies to halt or even reverse established lesion are not available yet. While numerous growth factors and environmental stimuli that drive progression of chronic kidney disease are present within the fibrotic microenvironment, the effector cells' genetic information needs to be accessible in order to enable the pro-fibrotic response. As more than 2 m of DNA encoding the genetic information is crammed as protein-DNA complex called chromatin within the nucleus of each cell, an accessible chromatin state is a prerequisite in the hierarchical order of events to enable production of fibrotic proteins and fibrotic cellular responses. Here, we review contribution and underlying mechanisms of chromatin organization, histone modifications and DNA methylation to progression of chronic kidney disease, provide recent evidence for cell type-specific cell fate decisions and discuss possible diagnostic and therapeutic applications.