1. Role of perivascular cells in kidney homeostasis, inflammation, repair and fibrosis.
- Author
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Tanaka, Shinji, Portilla, Didier, and Okusa, Mark D.
- Subjects
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PLATELET-derived growth factor , *RENAL fibrosis , *KIDNEY development , *KIDNEYS , *VASCULAR cell adhesion molecule-1 , *CHRONIC kidney failure - 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. Perivascular cells have beneficial roles that maintain kidney homeostasis but can also contribute to kidney pathology. Here, the authors focus mainly on pericytes and fibroblasts to examine these roles, including the contribution of perivascular cells to the myofibroblast pool in kidney fibrosis, and their crosstalk with tubular, immune and endothelial cells. Key points: Perivascular niches in the kidney comprise heterogeneous cell populations, including pericytes and fibroblasts, with distinct functions. These perivascular cells have crucial roles in maintaining homeostasis in the kidney. Pericytes maintain microvascular networks by stabilizing the vasculature and modulating the constriction of capillaries. In pathological states, such as ischaemia–reperfusion, pericytes contribute to the 'no-reflow' phenomenon. A subset of kidney perivascular cells can produce and secrete erythropoietin; hypoxia-inducible factor-prolyl hydroxylase inhibitors can boost this secretion and are used for the treatment of anaemia in chronic kidney disease. Perivascular cells or platelet-derived growth factor receptor-β+ (PDGFRβ+) pericytes synthesize and secrete various intracellular complement proteins and contribute to expression of collagen and extracellular matrix observed during the development of kidney fibrosis. In pathophysiological states, kidney perivascular cells contribute to the progression of kidney fibrosis, partly by transdifferentiating into myofibroblasts. Perivascular cells are major innate immune sentinels in the kidney and produce pro-inflammatory cytokines and chemokines after injury; these mediators promote immune cell infiltration, leading to persistent inflammation and progression of kidney fibrosis. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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