BACKGROUND & AIMS: Fibrosis is an abnormal extension of the wound healing process that follows tissue damage; it is involved in pathogenesis in a variety of chronic diseases. The formation of extracellular matrix is an essential response in wound healing. Although it has been proposed that collagen organization and assembly depend on the fibronectin matrix in culture, the contribution of fibronectin to these processes remains to be defined in vivo. METHODS: We generated a conditional, fibronectin-deficient mouse model of liver injury and explored whether fibronectin would be a suitable target for preventing extensive collagen deposits and scar formation that could lead to liver fibrosis. RESULTS: The lack of fibronectin did not interfere with reconstruction of collagen fibril organization in response to liver injury. Signaling by transforming growth factor-β and type V collagen were required for collagen fibrillogenesis during remodeling of adult liver tissue. CONCLUSIONS: Transforming growth factor-β and type V collagen are targets for regulating the initial fibrogenic response to liver damage.
BACKGROUND & AIMS:Fibrosis is an abnormal extension of the wound healing process that follows tissue damage; it is involved in pathogenesis in a variety of chronic diseases. The formation of extracellular matrix is an essential response in wound healing. Although it has been proposed that collagen organization and assembly depend on the fibronectin matrix in culture, the contribution of fibronectin to these processes remains to be defined in vivo. METHODS: We generated a conditional, fibronectin-deficient mouse model of liver injury and explored whether fibronectin would be a suitable target for preventing extensive collagen deposits and scar formation that could lead to liver fibrosis. RESULTS: The lack of fibronectin did not interfere with reconstruction of collagen fibril organization in response to liver injury. Signaling by transforming growth factor-β and type V collagen were required for collagen fibrillogenesis during remodeling of adult liver tissue. CONCLUSIONS: Transforming growth factor-β and type V collagen are targets for regulating the initial fibrogenic response to liver damage.
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