Department of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Bioengineered. 2021 Dec;12(1):1138-1149. doi: 10.1080/21655979.2021.1906097.
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.
整合素 β3（ITGβ3）-Ras 同源基因家族成员 A（RhoA）和 Yes 相关蛋白（YAP）轴在动脉粥样硬化中起重要作用。此外，在高糖（HG）暴露的足细胞中观察到 ITGβ3 过表达。然而，ITGβ3-RhoA-YAP 轴在 HG 诱导的足细胞损伤中的作用尚不清楚。本研究旨在探讨 ITGβ3 是否通过调节 RhoA-YAP 轴调节足细胞损伤。通过体外划痕愈合试验、流式细胞术、逆转录定量聚合酶链反应（RT-qPCR）和 Western blot 试验观察 ITGβ3 的功能和潜在机制。结果表明，HG 处理增加了伤口闭合和细胞凋亡的能力；然而，尽管进行了 HG 处理，ITGβ3 抑制减轻了足细胞的伤口闭合和细胞凋亡能力。相比之下，ITGβ3 的过表达增加了足细胞的伤口闭合和细胞凋亡能力。在 HG 处理下，ITGβ3 敲低与 RhoA、总 YAP1 和核 YAP1 的上调有关，而 ITGβ3 的过表达则有相反的效果。此外，在足细胞中过表达 RhoA 可逆转 ITGβ3 过表达对足细胞伤口闭合和细胞凋亡能力的影响，挽救 ITGβ3 过表达足细胞中 YAP 的表达。总之，ITGβ3 的过表达通过抑制 RhoA-YAP 轴促进足细胞损伤。这将为防止足细胞损伤提供新的线索。
