Alteration in distribution of focal adhesion components by signaling inhibitors in hepatic stellate cells and fibroblasts cultured on type I collagengel

Both hepatic stellate cells (HSCs) and fibroblasts exhibited an induction o f cytoplasmic processes in response to extracellular interstitial collagen. To elucidate the mechanism of process induction and sustenance, we examine d the effects of Signaling inhibition on process architecture and the distr ibution of focal adhesion components in HSC and fibroblast cultures. Inhibi tion of protein tyrosine (Tyr) kinase or phosphatidylinositol (PI) 3-kinase by staurosporin- and herbimycin A- or wortmannin-treatment, respectively, induced the retraction of elongated processes, and finally changed the cell s to round shapes in both cultures. The treatment with herbimycin A or wort mannin also affected the distribution of integrin alpha 2 subunit, focal ad hesion components such as vinculin and talin, and Tyr-phosphorylated protei ns. These results suggest that a similar mechanism, including protein and/o r PI kinase following integrin-binding to extracellular collagen fibrils, i s involved in the process elongation by F-actin and microtubule reorganizat ion in both HSCs and fibroblast cultured on type I collagen gel.