Transforming growth factor-β-inducible gene-h3 (βig-h3) promotes cell adhesion of human astrocytoma cells in vitro: Implication of α6β4 integrin

βig-h3 is a secretory protein that is induced by transforming growth factor (TGF)-β. We have recently found that βig-h3 expression is induced in cultured astrocytes by TGF-β1 and in rat cerebral cortex by stab wound. The purpose of this study was to examine the effect of the secreted βig-h3 on cell adhesion of astrocytes and the underlying mechanisms. When U87 human astrocytoma cells were seeded on dishes coated with recombinant βig-h3, cell adhesion was significantly enhanced. Blocking experiments using various antibodies to the integrin subunit suggested α6β4 integrin could be involved in the βig-h3-mediated astrocyte cell adhesion. Cell adhesion to βig-h3 substrate was substantially blocked by preincubation with the inhibitor to the src kinase. When cells were plated on βig-h3-coated dishes, tyrosine phosphorylation of focal adhesion kinase was prominently increased within 20 min in a β4 integrin-dependent manner. The results suggest that α6β4 integrin-mediated interactions of astrocytes with βig-h3 transduce intracellular signals through the focal adhesion proteins, which may regulate certain aspects of astrocyte response to brain injury.