ABSTRACT
Peritoneal fibrosis is one of the major complications occurring in long-term peritoneal dialysis patients as a result of injury. Peritoneal fibrosis is characterized by submesothelial thickening and fibrosis which is associated with a decline in peritoneal membrane function. The myofibroblast has been identified as the key player involved in the development and progression of peritoneal fibrosis. Activation of the myofibroblast is correlated with expansion of the extracellular matrix and changes in peritoneal membrane integrity. Over the years, epithelial to mesenchymal transition (EMT) has been accepted as the predominant source of the myofibroblast. Peritoneal mesothelial cells have been described to undergo EMT in response to injury. Several animal and in vitro studies support the role of EMT in peritoneal fibrosis; however, emerging evidence from genetic fate-mapping studies has demonstrated that myofibroblasts may be arising from resident fibroblasts and pericytes/perivascular fibroblasts. In this review, we will discuss hypotheses currently surrounding the origin of the myofibroblast and highlight the experimental systems predominantly being used to investigate this.
Subject(s)
Animals , Humans , Extracellular Matrix , Fibroblasts , Fibrosis , In Vitro Techniques , Membranes , Myofibroblasts , Peritoneal Dialysis , Peritoneal FibrosisABSTRACT
The increasing burden of chronic kidney disease worldwide and recent advancements in the understanding of pathologic events leading to kidney injury have opened up new potential avenues for therapies to further diminish progression of kidney disease by targeting the glomerular filtration barrier and reducing proteinuria. The glomerular filtration barrier is affected by many different metabolic and immune-mediated injuries. Glomerular endothelial cells, the glomerular basement membrane, and podocytes-the three components of the filtration barrier-work together to prevent the loss of protein and at the same time allow passage of water and smaller molecules. Damage to any of the components of the filtration barrier can initiate proteinuria and renal fibrosis. Transforming growth factor-beta (TGF-beta) is a pleiotropic cytokine strongly associated with the fibrogenic response.It has a known role in tubulointerstitial fibrosis. In this review we will highlight what is known about TGF-beta and how it interacts with the components of glomerular filtration barrier and causes loss of function and proteinuria.
Subject(s)
Endothelial Cells , Fibrosis , Filtration , Glomerular Basement Membrane , Glomerular Filtration Barrier , Kidney , Kidney Diseases , Podocytes , Proteinuria , Renal Insufficiency, Chronic , Transforming Growth Factor beta , WaterABSTRACT
The increasing burden of chronic kidney disease worldwide and recent advancements in the understanding of pathologic events leading to kidney injury have opened up new potential avenues for therapies to further diminish progression of kidney disease by targeting the glomerular filtration barrier and reducing proteinuria. The glomerular filtration barrier is affected by many different metabolic and immune-mediated injuries. Glomerular endothelial cells, the glomerular basement membrane, and podocytes-the three components of the filtration barrier-work together to prevent the loss of protein and at the same time allow passage of water and smaller molecules. Damage to any of the components of the filtration barrier can initiate proteinuria and renal fibrosis. Transforming growth factor-beta (TGF-beta) is a pleiotropic cytokine strongly associated with the fibrogenic response.It has a known role in tubulointerstitial fibrosis. In this review we will highlight what is known about TGF-beta and how it interacts with the components of glomerular filtration barrier and causes loss of function and proteinuria.