Role of perivascular cells in kidney homeostasis, inflammation, repair and fibrosis

Abstract

Perivascular niches in the kidney comprise heterogeneous cell populations, including pericytes and fibroblasts, with distinct functions. These perivascular cells have crucial roles in preserving kidney homeostasis as they maintain microvascular networks by stabilizing the vasculature and regulating capillary constriction. A subset of kidney perivascular cells can also produce and secrete erythropoietin; this ability can be enhanced with hypoxia-inducible factor-prolyl hydroxylase inhibitors, which are used to treat anaemia in chronic kidney disease. In the pathophysiological state, kidney perivascular cells contribute to the progression of kidney fibrosis, partly via transdifferentiation into myofibroblasts. Moreover, perivascular cells are now recognized as major innate immune sentinels in the kidney that produce pro-inflammatory cytokines and chemokines following injury. These mediators promote immune cell infiltration, leading to persistent inflammation and progression of kidney fibrosis. The crosstalk between perivascular cells and tubular epithelial, immune and endothelial cells is therefore a key process in physiological and pathophysiological states. Here, we examine the multiple roles of kidney perivascular cells in health and disease, focusing on the latest advances in this field of research.