Fibrosis of the glomerular and/or tubulointerstitial compartments is a hallmark of progressive kidney disease and is considered to be a major pathway leading to end-stage of renal failure. Fibrogenesis of the kidney is a dynamic process that initially involves the recruitment and activation of leukocytes (e.g. macrophages and T cells) and activation of intrinsic kidney cells (e.g. mesangial cells, tubular epithelial cells, and fibroblasts). This is followed by production and deposition of excessive amounts of extracellular matrix which progressively replaces normal renal structure and results in loss of function. Fibrosis is potentially reversible if the underlying insult can be resolved, but this is seldom the case and thus we need to understanding the complex mechanisms underlying progressive fibrosis of the glomerular and tubulointerstitial compartments. Collagen producing fibroblasts/myofibroblasts play a key role in fibrosis; however, they may derive from multiple sources through diverse mechanisms, including; activation of interstitial fibroblasts and pericytes, phenotypic conversion of tubular epithelial cells or endothelial cells to myofibroblasts, and from extra-renal sources such as bone marrow fibrocytes. Studies of the contribution of these different myofibroblast precursor populations have focused on two models of tubulointerstitial fibrosis, leaving unanswered questions in models of glomerular disease and a lack of data in human kidney disease. A number of soluble factors and intracellular signaling pathways have been shown to contribute to the development of renal fibrosis, including: transforming growth factor-ß (TGF-ß), Wnt/ß-catenin, bone morphogenic proteins (BMP), platelet-derived growth factors (PDGF), fibroblast growth factors (FGF), notch proteins, integrins, renin angiotensin-aldosterone system, and endothelin. Recent genomic approaches have also shed insight into the molecular pathways regulating renal fibrosis. Thus, in this specific research topic, we outline the current understanding of the cellular and molecular mechanisms of renal fibrosis. We also describe the development of new therapeutic strategies for renal fibrosis.
Fibrosis of the glomerular and/or tubulointerstitial compartments is a hallmark of progressive kidney disease and is considered to be a major pathway leading to end-stage of renal failure. Fibrogenesis of the kidney is a dynamic process that initially involves the recruitment and activation of leukocytes (e.g. macrophages and T cells) and activation of intrinsic kidney cells (e.g. mesangial cells, tubular epithelial cells, and fibroblasts). This is followed by production and deposition of excessive amounts of extracellular matrix which progressively replaces normal renal structure and results in loss of function. Fibrosis is potentially reversible if the underlying insult can be resolved, but this is seldom the case and thus we need to understanding the complex mechanisms underlying progressive fibrosis of the glomerular and tubulointerstitial compartments. Collagen producing fibroblasts/myofibroblasts play a key role in fibrosis; however, they may derive from multiple sources through diverse mechanisms, including; activation of interstitial fibroblasts and pericytes, phenotypic conversion of tubular epithelial cells or endothelial cells to myofibroblasts, and from extra-renal sources such as bone marrow fibrocytes. Studies of the contribution of these different myofibroblast precursor populations have focused on two models of tubulointerstitial fibrosis, leaving unanswered questions in models of glomerular disease and a lack of data in human kidney disease. A number of soluble factors and intracellular signaling pathways have been shown to contribute to the development of renal fibrosis, including: transforming growth factor-ß (TGF-ß), Wnt/ß-catenin, bone morphogenic proteins (BMP), platelet-derived growth factors (PDGF), fibroblast growth factors (FGF), notch proteins, integrins, renin angiotensin-aldosterone system, and endothelin. Recent genomic approaches have also shed insight into the molecular pathways regulating renal fibrosis. Thus, in this specific research topic, we outline the current understanding of the cellular and molecular mechanisms of renal fibrosis. We also describe the development of new therapeutic strategies for renal fibrosis.
