Pivotal role of pericytes in kidney fibrosis

Abstract

1. Kidney pericytes were recently identified as collagen Iα1-producing cells in healthy kidney, but the developmental, physiological and pathological roles of kidney pericytes remain poorly understood. Pericytes are stromal-derived cells that envelop and have intimate connections with adjacent capillary endothelial cells (EC). Recent studies in the eye and brain have revealed that pericytes are crucial for angiogenesis, vascular stability and vessel integrity. 2. In response to kidney injury, pericytes promptly migrate away from the capillary wall into the interstitial space. Here, pericytes are activated and differentiate into scar-forming myofibroblasts. In the absence of pericytes, peritubular capillaries are destabilized, leading to vascular regression. Consequently, capillary loss and fibrosis following kidney injury are intimately linked and hinge centrally around pericyte detachment from EC. 3. Kinetic mathematical modelling has demonstrated that pericytes are the major source of myofibroblasts in the fibrotic kidney. Comprehensive genetic fate mapping studies of nephron epithelia or kidney stroma has demonstrated that epithelial cells do not migrate outside of the epithelial compartment to become myofibroblasts; rather, interstitial pericytes are progenitors of scar-forming myofibroblasts. Bidirectional signalling between pericytes and EC is necessary for pericyte detachment from peritubular capillaries. 4. In the present review, we summarize the pathologically vital roles of kidney pericytes in fibrosis, including our new findings. The study of kidney pericytes and endothelial-pericyte cross-talk will identify novel therapeutic targets for currently incurable chronic kidney diseases.