Abstract
Many physiological and pathophysiological processes in cells or tissues are involving mechanical stretch, which is inducing gap junction gene expression and cytokine TGF beta changes. However, the underlying mechanisms of gap junction gene expression changes remain unknown. Here, we showed that the expression of Cx43 at mRNA and protein level in Human umbilical-vein endothelial cells (HUVECs) is significantly increased after 24 h stretch stimulation, and TGF beta1, but not TGF beta2 expression is also upregulated. Administration of TGF betal into HUVECs without stretch also induced upregulation of Cx43 mRNA and protein expression. While simultaneously administration of TGF beta1 with SB431542, a specific inhibitor of TGF beta1 receptor, blocked the Cx43 protein upregulation by TGF beta1. Further, the increase of Cx43 protein expression under stretch condition can be partially blocked by SB431542; moreover, it also can be partially blocked by simultaneously administration of anti-TGF beta1 monoclonal neutralization antibody. Importantly, the stretch induced upregulation of Cx43 can be blocked by administration of actin and microtubule inhibitors, while NEDD4, a key element in mediating Cx43 protein ubiquitination and degradation, is not changed under stretch condition. Therefore, we conclude that upregulation of Cx43 expression under 24 h stretch condition is mediated by TGF beta1 via TGF beta1 receptor signaling pathway, and it also involves the actin and microtubule cytoskeletal network.