PDGFR ‐β and kidney fibrosis

Abstract

Chronic kidney disease (CKD) is one of the fastest growing global causes of death, estimated to rank among the top five by 2040 (Foreman et al, 2018). This illustrates current pitfalls in diagnosis and management of CKD. Advanced CKD requires renal function replacement by dialysis or transplantation. However, earlier CKD stages, even when renal function is still normal, are already associated with an increased risk of premature death (Perez‐Gomez et al, 2019). Thus, novel approaches to diagnose and treat CKD are needed. The histopathological hallmark of CKD is kidney fibrosis, which is closely associated with local inflammation and loss of kidney parenchymal cells. Thus, kidney fibrosis is an attractive process to develop tests allowing an earlier diagnosis of CKD and represents a potential therapeutic target to slow CKD progression or promote regression.

Pyruvate kinase M2 regulates kidney fibrosis through pericyte glycolysis during the progression from acute kidney injury to chronic kidney disease

“…As a prognostic indicator of AKI, kidney fibrosis affects millions of people worldwide 20 . Renal pericytes play an important role in the progression of kidney fibrosis 3 . In the healthy kidney, renal pericytes interact with vascular endothelial cells to regulate blood flow.…”

“…A meta‐analysis of 82 studies showed that the risk of chronic kidney disease (CKD) in AKI patients increased by 2.67 times, the risk of end‐stage renal disease increased by 4.81 times, and the risk of death increased by 1.80 times 2 . Renal interstitial fibrosis is a key feature of AKI‐to‐CKD progression, and the secretion of extracellular matrix components by myofibroblasts plays an important role in renal interstitial fibrosis 3 . Genetic fate tracing studies have shown that renal pericytes in the renal interstitium are a major source of myofibroblasts during fibrotic nephropathy 4,5 .…”

“… 2 Renal interstitial fibrosis is a key feature of AKI‐to‐CKD progression, and the secretion of extracellular matrix components by myofibroblasts plays an important role in renal interstitial fibrosis. 3 Genetic fate tracing studies have shown that renal pericytes in the renal interstitium are a major source of myofibroblasts during fibrotic nephropathy. 4 , 5 However, the characteristics of pericyte fate and transition during AKI‐CKD still need to be further elucidated.…”

Inducible deletion of microRNA activity in kidney mesenchymal cells exacerbates renal fibrosis

“…Platelet-derived growth factor receptor-β (PDGFR-β) is constitutively expressed in interstitial fibroblasts, mesangial cells, vascular smooth muscle cells, and pericytes 6 . PDGFR-β is a tyrosine-kinase receptor for platelet-derived growth factor (PDGF)-B and PDGF-D. On activation, PDGFR-β induces downstream signaling that triggers cell proliferation, migration, and differentiation 6 . Transgenic mice with PDGFR-β activation in renal mesenchymal cells had mesangioproliferative glomerulonephritis, mesangial sclerosis, and interstitial fibrosis 7 .…”

Mesenchymal Stem Cell-Derived Exosome miR-21-3p Prevents Renal Fibrosis

“…The high incidence of chronic kidney disease (CKD) brings heavy economic burden to the society and patients' families [1]. It is generally believed that the destruction of normal renal parenchyma caused by brosis is a common pathogenic factor leading to progressive damage in CKD [2,3]. Although a serious of studies have found the key cellular and molecular mediators that lead to brosis, they have not been clinically veri ed.…”