A mechanistic overview on liver fibrogenesis
Keywords:Liver Fibrogenesis, Hepatic Stellate Cell, Fibroblast, Hypoxia, Extra Cellular Matrix
Liver wound healing process, fibrosis consists of many sequential steps such as inflammation, deposition of extracellular matrix and initiation of neovascularization. Liver damage leads to an inflammatory response through the activation and proliferation of Mesenchymal cell populations within the liver, which further remodel the extracellular matrix as a part of healing response. While chronic damage accumulates scarring proteins (fibrosis) that alters tissue structure and function leading to cirrhosis. Pathological angiogenesis is associated with the fibrogenic progression which eventually leads to the development of cirrhosis and liver failure. Identification of hepatic stellate cell (HSC) as the major fibrogenic cell type in the injured liver unearthed the role of HSC in the progression fibrogenesis and becomes a target for drug development. Multiple etiologies of liver disease lead to liver fibrosis through integrated signaling networks driven by the HSC. On pathological stimulation HSC changes its phenotype into a myofibroblast like phenotype that is contractile, proliferative and fibrogenic. Collagen and other extracellular matrix (ECM) components are deposited as the liver initiates a wound healing response. Sustained fibrogenesis leads to cirrhosis, characterized by the distortion of the liver parenchyma and vascular architecture. In this review, we briefly summarize the current knowledge about liver fibrogenesis and its resolution on liver damage. This review has also described the prominent new mechanisms of liver fibrosis and highlighted signaling pathways that are being actively studied. Steady advances in understanding how to exploit various signaling pathways towards fibrosis regression is creating realistic hopes for effective anti-fibrotic therapies.
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