Claudia Schrimpf1, Jeremy S Duffield. 1. Laboratory of Inflammation Research, Renal Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Abstract
PURPOSE OF REVIEW: Until recently kidney pericytes were little known. This review will update readers about key new findings concerning pericyte abundance, function in kidney vascular biology and major role in fibrogenesis. Moreover readers will become familiar with the central role of pericyte-endothelial interactions in peritubular capillary health or rarefaction and the pivotal role these may play in renal ischemia. RECENT FINDINGS: Pericytes are stromal cells that partially cover capillary walls. Pericytes were recently identified as collagen-1α1 producing cells in healthy adult kidney. Kinetic mathematical modeling studies indicated they were the source of scar-forming myofibroblasts. Comprehensive fate mapping of kidney stroma confirmed that pericytes and perivascular fibroblasts, not epithelium, were the major source of myofibroblasts. Blockade of pericyte-endothelial cross-talk in response to renal injury prevents both microvascular rarefaction and interstitial fibrosis. The detachment of pericytes from endothelium under pathological conditions and differentiation into myofibroblasts leads to pericyte deficiency at the microvascular interstitial interface, resulting in unstable microvasculature and thence vessel rarefaction, ultimately leading to nephron ischemia. To develop new therapeutic strategies, a better understanding of not only pericyte detachment and migration from capillaries, but also pericyte-endothelial crosstalk in health and injury is required. SUMMARY: This review summarizes the functional role of pericytes during fibrosis, focusing on myofibroblast origins and pericyte-endothelial cross-talk.
PURPOSE OF REVIEW: Until recently kidney pericytes were little known. This review will update readers about key new findings concerning pericyte abundance, function in kidney vascular biology and major role in fibrogenesis. Moreover readers will become familiar with the central role of pericyte-endothelial interactions in peritubular capillary health or rarefaction and the pivotal role these may play in renal ischemia. RECENT FINDINGS: Pericytes are stromal cells that partially cover capillary walls. Pericytes were recently identified as collagen-1α1 producing cells in healthy adult kidney. Kinetic mathematical modeling studies indicated they were the source of scar-forming myofibroblasts. Comprehensive fate mapping of kidney stroma confirmed that pericytes and perivascular fibroblasts, not epithelium, were the major source of myofibroblasts. Blockade of pericyte-endothelial cross-talk in response to renal injury prevents both microvascular rarefaction and interstitial fibrosis. The detachment of pericytes from endothelium under pathological conditions and differentiation into myofibroblasts leads to pericyte deficiency at the microvascular interstitial interface, resulting in unstable microvasculature and thence vessel rarefaction, ultimately leading to nephron ischemia. To develop new therapeutic strategies, a better understanding of not only pericyte detachment and migration from capillaries, but also pericyte-endothelial crosstalk in health and injury is required. SUMMARY: This review summarizes the functional role of pericytes during fibrosis, focusing on myofibroblast origins and pericyte-endothelial cross-talk.
Authors: Gabriela Campanholle; Giovanni Ligresti; Sina A Gharib; Jeremy S Duffield Journal: Am J Physiol Cell Physiol Date: 2013-01-16 Impact factor: 4.249
Authors: Craig B Woda; Sarah Bruneau; Anne Linde Mak; Zdenka Haskova; Kaifeng Liu; Chandra C Ghosh; David M Briscoe Journal: Biochem Biophys Res Commun Date: 2019-09-18 Impact factor: 3.575