COL1A1 expression induced by overexpression of both a 15-amino acid peptide from the fibrinogen domain of tenascin-X and integrin α11 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 α11, 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 α11 induced the expression of type I collagen α1 chain (COL1A1). Treatment with verteporfin [YAP (Yes-associated protein) inhibitor] attenuated the elevated COL1A1 expression elicited by overexpression of both hTNX-FGFFFF and integrin α11. 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 α11. These results indicated that overexpression of both hTNX-FGFFFF and integrin α11 induced COL1A1 expression via the YAP signaling pathway.