The role played by perivascular cells in kidney interstitial injury

Abstract

Fibrosis of the kidney is a disease affecting millions worldwide and is a harbinger of progressive loss of organ function resulting in organ failure. Recent findings suggest that understanding mechanisms of development and progression of fibrosis will lead to new therapies urgently required to counteract loss of organ function. Recently, little-known cells that line the kidney microvasculature, known as pericytes, were identified as the precursor cells which become the scar-forming myofibroblasts. Kidney pericytes are extensively branched cells located in the wall of capillaries, embedded within the microvascular basement membrane, and incompletely envelope endothelial cells with which they establish focal contacts. In response to kidney injuries, pericytes detach from endothelial cells and migrate into the interstitial space where they undergo a transition into myofibroblasts. Detachment leads to fibrosis but also leaves an unstable endothelium, prone to rarefaction. Endothelial-pericyte crosstalk at the vascular endothelial growth factor receptors and platelet derived growth factor receptors in response to injury have been identified as major new targets for therapeutic intervention.

Renal Aging: Causes and Consequences

“…Pericyte-endothelial detachment under pathologic conditions and their differentiation into myofibroblasts promote microvascular rarefaction, hypoxia, and fibrosis. 125,126 Proposed mediators of this pericyte-endothelial crosstalk include VEGF and PDGF, 127 and blocking this pericyte-endothelial interaction attenuates microvascular damage and interstitial fibrosis. 128,129…”

The Renal Endothelium in Diabetic Nephropathy

“…In models of kidney injury, targeting crosstalk between endothelial cells and pericytes by inhibiting VEGF receptors or PDGF receptors reduced interstitial fibrosis and peritubular capillaries rarefaction. [114][115][116][117] The role of interaction between peritubular capillaries endothelial cells and pericytes in diabetic nephropathy remains to be elucidated.…”

Cellular Mechanisms of Tissue Fibrosis. 3. Novel mechanisms of kidney fibrosis

“…Pericytes can be distinguished from perivascular fibroblasts (also known as fibrocytes or adventitial cells), which surround arterioles and have no connection with endothelium (83). They can also be distinguished from VSMCs, which surround larger blood vessels, by their location, since VSMCs are separated from endothelial cells by an internal elastic lamina and do not completely share molecular marker expression (83,87). Several recent reviews provide a list of validated markers to identify pericytes including those mentioned above (83,87).…”