COL1A1 expression induced by overexpression of both a 15-amino acid peptide from the fibrinogen domain of tenascin-X and integrin [alpha]11 in LX-2 cells

Extracellular matrix tenascin-X (TNX) is the largest member of the tenascin family. Our previous study demonstrated that TNX was involved in hepatic dysfunction, including fibrosis, in mice that were administered a high-fat and high-cholesterol diet with high levels of phosphorus and calcium. The present study investigated whether overexpression of both the fibrinogen domain of TNX (TNX-FG) and integrin [alpha]11, one of the TNX cell surface receptors, induces in vitro fibrosis in LX-2 human hepatic stellate cells. Overexpression of both a 15-amino acid peptide (hTNX-FGFFFF) derived from the TNX-FG domain and integrin [alpha]11 induced the expression of type I collagen a1 chain (COL1A1). Treatment with verteporfin [YAP (Yes-associated protein) inhibitor] attenuated the elevated COL1A1 expression elicited by overexpression of both hTNX-FGFFFF and integrin [alpha]11. In addition, small interfering RNA-mediated knockdown of YAP1 resulted in a decrease in COL1A1 expression induced by overexpression of both hTNX-FGFFFF and integrin [alpha]11. These results indicated that overexpression of both hTNX-FGFFFF and integrin [alpha]11 induced COL1A1 expression via the YAP signaling pathway. Key words: type I collagen al chain, fibrosis, integrin [alpha]11[beta]1, tenascin-X, Yes-associated protein