A Fibronectin-Independent Mechanism of Collagen Fibrillogenesis in Adult Liver Remodeling

作者：Moriya Kei; Bae Eunnyung; Honda Kazuhisa; Sakai Keiko; Sakaguchi Takehisa; Tsujimoto Ikuko; Kamisoyama Hiroshi; Keene Douglas R; Sasaki Takako; Sakai Takao^*

来源：Gastroenterology, 2011, 140(5): 1653-1663.

DOI：10.1053/j.gastro.2011.02.005

• Liver Disease
• Hepatic Stellate Cells
• Mouse Model of Fibrosis
• Conditional Knockout

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-beta and type V collagen were required for collagen fibrillogenesis during remodeling of adult liver tissue. CONCLUSIONS: Transforming growth factor-beta and type V collagen are targets for regulating the initial fibrogenic response to liver damage.

• 出版日期2011-5