Fibrosis and cirrhosis reversibility - molecular mechanisms.
The concept that liver fibrosis is a dynamic process with potential for regression as well as progression has emerged in parallel with clinical evidence for remodeling of fibrotic extracellular matrix in patients who can be effectively treated for their underlying cause of liver disease. This article reviews recent discoveries relating to the cellular and molecular mechanisms that regulate fibrosis regression, with emphasis on studies that have used experimental in vivo models of liver disease. Apoptosis of hepatic myofibroblasts is discussed. The functions played by transcription factors, receptor-ligand interactions, and cell-matrix interactions as regulators of the lifespan of hepatic myofibroblasts are considered, as are the therapeutic opportunities for modulating these functions. Growth factors, proteolytic enzymes, and their inhibitors are discussed in detail.
Gieling
Roben G
RG
Liver Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Burt
Alastair D
AD
Mann
Derek A
DA
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000473:pathology / Q000502:physiology; D006801:Humans; D008099:Liver / Q000098:blood supply / Q000378:metabolism; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000503:physiopathology; D020127:Recovery of Function; D015398:Signal Transduction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
D016328:NF-kappa B; D019715:Tissue Inhibitor of Metalloproteinase-1; D020782:Matrix Metalloproteinases