Integrin β3 overexpression contributes to podocyte injury through inhibiting RhoA/YAP signaling pathway.

Axis formed by integrin β3 (ITGβ3)-Ras homolog gene family, member A (RhoA), and Yes-associated protein (YAP) plays an important role in atherosclerosis. In addition, ITGβ3 overexpression was noted in high-glucose (HG) exposure podocytes. However, the ITGβ3-RhoA-YAP axis on HG-induced podocyte injury remains unclear. This study aimed to investigate whether ITGβ3 regulates podocyte injury by regulating the RhoA-YAP axis. The function and potential mechanism of ITGβ3 were observed through in vitro wound-healing assays, flow cytometry, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and western blot assay. Results showed that HG treatment increased the ability of wound closure and apoptosis; however, in spite of HG treatment, ITGβ3 inhibition mitigated the ability of wound closure and apoptosis in podocytes. By contrast, overexpression of ITGβ3 increased the wound closure and apoptosis abilities of podocytes. Under HG treatment, ITGβ3 knockdown is associated with upregulation of RhoA, total YAP1, and nucleus YAP1, whereas ITGβ3 overexpression has opposite effect. In addition, RhoA overexpression in podocytes reverses the effect of ITGβ3 overexpression on the wound closure and apoptosis abilities of podocytes, rescue the expression of YAP in ITGβ3 overexpression podocytes. Taken together, ITGβ3 overexpression promotes podocytes injury by inhibiting RhoA-YAP axis. This will provide a new clue for preventing podocyte from damage.