TGF-β Signaling Induces the Expression of OPN in Blood Vessel Endothelial Cells

Background: The mechanism of blood vessel formation and degeneration still remains unclear. Transforming growth factor-beta 1 (TGF-beta 1) signaling is a critical pathway in this progression and can induce multiple biological effects. Osteopontin (OPN) is involved in mineral metabolism and the inflammatory response associated with vascular calcification. Methods: To identify the relationship between TGF-beta signaling pathway and OPN, we stimulated human vascular endothelial cells (HVECs) and human aortic endothelial cells (HAECs) using various concentration of TGF-beta 1 in vitro. Results: As assessed by flow cytometry and western blots, apoptosis levels were significantly increased with TGF-beta 1 treatment. We also demonstrated that OPN increased in vitro with TGF-beta signaling by western blot and quantitative real time polymerase chain reaction (qRT-PCR) analyses. The inhibitory phosphorylation of endothelial nitric-oxide synthase (eNOS) (Thr495) was also up-regulated by TGF-beta signaling. Meanwhile, the anti-inflammatory factor Nrf2 and the activating phosphorylation of eNOS (Ser1177) were down-regulated. Conclusions: Taken together, our findings demonstrate that TGF-beta signaling can induce the expression of OPN, which may play an important role in the dysfunction of the vascular wall.