Integrin Beta 3 Overexpression Contributes To Podocyte Injury Through Inhibiting Rhoa/Yap Signaling Pathway

Axis formed by integrin beta 3 (ITG beta 3)-Ras homolog gene family, member A (RhoA), and Yes-associated protein (YAP) plays an important role in atherosclerosis. In addition, ITG beta 3 overexpression was noted in high-glucose (HG) exposure podocytes. However, the ITG beta 3-RhoA-YAP axis on HG-induced podocyte injury remains unclear. This study aimed to investigate whether ITG beta 3 regulates podocyte injury by regulating the RhoA-YAP axis. The function and potential mechanism of ITG beta 3 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, ITG beta 3 inhibition mitigated the ability of wound closure and apoptosis in podocytes. By contrast, overexpression of ITG beta 3 increased the wound closure and apoptosis abilities of podocytes. Under HG treatment, ITG beta 3 knockdown is associated with upregulation of RhoA, total YAP1, and nucleus YAP1, whereas ITG beta 3 overexpression has opposite effect. In addition, RhoA overexpression in podocytes reverses the effect of ITG beta 3 overexpression on the wound closure and apoptosis abilities of podocytes, rescue the expression of YAP in ITG beta 3 overexpression podocytes. Taken together, ITG beta 3 overexpression promotes podocytes injury by inhibiting RhoA-YAP axis. This will provide a new clue for preventing podocyte from damage.