TGF-β-induced protein βig-h3 is upregulated by high glucose in vascular smooth muscle cells

TGF-β-induced gene-h3 (βig-h3) is an adhesive molecule that interacts with integrins. Because TGF-β plays an important role in diabetic complications and βig-h3 serves as a cell substrate, we hypothesized that diabetic conditions might increase βig-h3 synthesis in vascular smooth muscle cells (VSMCs), which may subsequently contribute to the pathogenesis of diabetic angiopathy. The concentrations of βig-h3 and TGF-β were measured in conditioned media using an enzyme-linked immunosorbent assay. An immunohistochemical study showed that βig-h3 was expressed in the VSMCs and the matrix of rat aortas. TGF-β stimulated βig-h3 production, and high glucose induced βig-h3 as well as TGF-β production in the VSMCs. The high glucose-induced βig-h3 expression was almost entirely blocked by an anti-TGF-β antibody. βig-h3 protein mediated the adhesion, spreading, migration, and proliferation of rat VSMCs. These results suggest that the high glucose-induced βig-h3 in VSMCs regulates VSMC functions and may play an important role in diabetic angiopathy.