Expression and function of integrin receptors for collagen and laminin in cultured human hepatic stellate cells

Background & Aims: Human hepatic stellate cells (HSCs), liver-specific pericytes, are currently considered major producers of extracellular matrix (ECM) components and key elements in the development of liver fibrogenesis. However, little is known about the possible functional interactions between HSCs and the various ECM components. Therefore, the present study was designed to evaluate the expression of integrins, the major family of extracellular matrix receptors. Methods: Integrin expression was evaluated by immunoprecipitation and confirmed by immunocytochemistry and flow cytometry. Results: Human HSCs were shown to express alpha(1) beta(1), alpha(2) beta(1), alpha(v) beta(1). Adhesion to type IV collagen, type I collagen, fibronectin, and laminin 1 was inhibited by anti-beta(1) antibody identifying beta(1)-containing integrins as possible receptors for these components. In addition, we showed that HSCs express alpha(6) beta(4), a heterodimer known to mediate adhesion of epithelial cells to laminin and not previously characterized in mesenchymal cells. Adhesion to laminin 1 was not inhibited by antibodies specific for alpha(6) or beta(4), thus establishing that laminin 1 is not a ligand for alpha(6) beta(4) in this cell type. Conclusions: These findings represent the first description of integrin receptors in HSC and provide an attempt to cover the gap of information in the field of HSC-ECM interactions.