title: Mitogen activated protein kinases in renal fibrosis.
abstract: The mitogen-activated protein (MAP) kinases are involved in both normal renal physiology and in the pathology of various forms of kidney injury, including renal fibrosis. In vitro studies have shown a role for all three MAP kinase (ERK, p38 and JNK) in the production of the major pro-fibrotic factor, transforming growth factor-beta1 (TGF-beta1) by intrinsic renal cell types. There is also considerable cross-talk between TGF-beta1 and MAP kinase signalling pathways in the synthesis and turnover of extracellular matrix by fibroblast-like cells in the kidney. In addition, MAP kinase signalling contributes to TGF-beta1 induced transition of tubular epithelial cells into myofibroblasts. Administration of specific inhibitors of individual MAP kinases has identified a pathogenic role for both p38 and JNK pathways in animal models of renal fibrosis. There is also evidence to suggest that MAP kinases are activated in human renal fibrosis. Thus, blockade of p38 and JNK pathways may have therapeutic potential for the treatment of chronic renal fibrosis.
authors.affiliation: Department of Nephrology and Monash University Department of Medicine, Monash Medical Centre, Clayton, Victoria, 3168, Australia.
authors.forename: Frank Y
authors.initials: FY
authors.lastname: Ma
authors.forename: Mythily
authors.initials: M
authors.lastname: Sachchithananthan
authors.forename: Robert S
authors.initials: RS
authors.lastname: Flanc
authors.forename: David J
authors.initials: DJ
authors.lastname: Nikolic-Paterson
mesh_terms: D000818:Animals; D005355:Fibrosis; D006801:Humans; D007674:Kidney Diseases / Q000201:enzymology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D020928:Mitogen-Activated Protein Kinases