Cellular and molecular mechanisms in kidney fibrosis

Abstract

Fibrosis is a characteristic feature of all forms of chronic kidney disease. Deposition of pathological matrix in the interstitial space and within the walls of glomerular capillaries as well as the cellular processes resulting in this deposition are increasingly recognized as important factors amplifying kidney injury and accelerating nephron demise. Recent insights into the cellular and molecular mechanisms of fibrogenesis herald the promise of new therapies to slow kidney disease progression. This review focuses on new findings that enhance understanding of cellular and molecular mechanisms of fibrosis, the characteristics of myofibroblasts, their progenitors, and molecular pathways regulating both fibrogenesis and its resolution.

Mechanisms of Lung Fibrosis Resolution

“…3 In the kidney, established glomerulosclerosis is reversible, and the interstitial matrix can resolve. 4 Studies in rodents demonstrate reversal of liver fibrosis in the experimental models of carbon tetrachloride or alcohol intoxication and bile duct ligation. 5 Although fibrosis regresses in these models, it is not fully reversible in advanced disease.…”

Renal Allograft Fibrosis: Biology and Therapeutic Targets

“…Embryonically fibroblasts and pericytes originate from the metanephric mesenchyme and Foxd1 progenitors (22,24). Other embryonic sources were also proposed, for example from protein zero (P0) neural crest progenitors (166).…”

“…Other embryonic sources were also proposed, for example from protein zero (P0) neural crest progenitors (166). A considerable number of studies have tackled the source of myofibroblasts during renal fibrosis (22,62,67,83,(172)(173)(174)(175)(176)(177)(178). In short, and in our opinion, the majority, if not all myofibroblasts arise from resident interstitial mesenchymal cells.…”

“…Thus, we present a subjective and non-comprehensive selection of recent work, focusing, wherever possible, on the allograft situation. The interested reader is referred to a number of recent reviews for further information (20)(21)(22)(23)(24)(25)(26).…”

Sonic hedgehog signaling in kidney fibrosis: a master communicator

“…From a cell biological standpoint, the intricate process of renal fibrosis has been linked, more or less, to an inappropriate activation of some key signaling pathways, such as transforming growth factor-β (TGF-β), renin-angiotensin system (RAS), Wnt/β-catenin, and sonic hedgehog (Shh) (He and Dai, 2015; Meng et al, 2015; Santos et al, 2012; Sweetwyne et al, 2014; Tan et al, 2014). Most of the time, these diverse signals reciprocally crosstalk through cell-to-cell communication that involves all resident cells in the kidney, as well as the infiltrating cells (Duffield, 2014; Liu, 2011; Zeisberg and Neilson, 2010). In the past several years, the role and mechanisms of TGF-β, RAS and Wnt/β-catenin signaling in the pathogenesis of CKD have been well documented (Meng et al, 2015; Sweetwyne et al, 2014; Tan et al, 2014; Zhou et al, 2015).…”