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 f ibrogenesis. However, little is known about the possible functional in teractions between HSCs and the various ECM components. Therefore, the present study was designed to evaluate the expression of integrins, t he major family of extracellular matrix receptors. Methods: Integrin e xpression was evaluated by immunoprecipitation and confirmed by immuno cytochemistry and flow cytometry. Results: Human HSCs were shown to ex press alpha(1) beta(1), alpha(2) beta(1), alpha(v) beta(1). Adhesion t o type IV collagen, type I collagen, fibronectin, and laminin 1 was in hibited by anti-beta(1) antibody identifying beta(1)-containing integr ins as possible receptors for these components. In addition, we showed that HSCs express alpha(6) beta(4), a heterodimer known to mediate ad hesion of epithelial cells to laminin and not previously characterized in mesenchymal cells. Adhesion to laminin 1 was not inhibited by anti bodies specific for alpha(6) or beta(4), thus establishing that lamini n 1 is not a ligand for alpha(6) beta(4) in this cell type. Conclusion s: These findings represent the first description of integrin receptor s in HSC and provide an attempt to cover the gap of information in the field of HSC-ECM interactions.