TNF alpha-Erk1/2 signaling pathway-regulated SerpinE1 and SerpinB2 are involved in lipopolysaccharide-induced porcine granulosa cell proliferation

文献类型： 外文期刊

第一作者： Qu, Xiaolu

作者： Qu, Xiaolu;Qu, Xiaolu;Guo, Shuangshuang;Yan, Leyan;Zhu, Huanxi;Li, Hui;Shi, Zhendan;Qu, Xiaolu;Guo, Shuangshuang;Yan, Leyan;Zhu, Huanxi;Li, Hui;Shi, Zhendan

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关键词： LPS; Granulosa cell; Proliferation; SerpinE1; SerpinB2

期刊名称：CELLULAR SIGNALLING （ 影响因子：4.315； 五年影响因子：4.206 ）

ISSN： 0898-6568

年卷期： 2020 年 73 卷

页码：

收录情况： SCI

摘要： Lipopolysaccharide (LPS) is an inhibitory factor that causes hormonal imbalance and subsequently affects ovarian function and fertility in mammals. Previous studies have shown that the exposure of granulosa cells (GC) to LPS leads to steroidogenesis dysfunction. However, the effects of LPS on the viability of GC remain largely unclear. In the present study, we aimed to address this question and unveil the underlying molecular mechanisms using cultured porcine GC. Results showed that GC proliferation and tumor necrosis factor alpha (TNF alpha) secretion were significantly increased after exposure to LPS, and these effects were completely reversed by blocking the TNF alpha sheddase, ADAM17. Moreover, GC proliferation induced by LPS was mimicked by treatment with recombinant TNF alpha. In addition, SerpinE1 and SerpinB2 expression levels increased in GC after treatment with LPS or recombinant TNF alpha, whereas blocking the Erk1/2 pathway completely abolished these effects and also inhibited GC proliferation. Further, consistent with the effects of blocking the Erk1/2 pathway, cell proliferation was completely inhibited by knocking down SerpinE1 or SerpinB2 in the presence of LPS or recombinant TNF alpha. Mitochondrial membrane potential (MMP) polarization in GC was increased by LPS or recombinant TNF alpha treatment, and these changes were completely negated by Erk1/2 inhibition, but not by SerpinE1 or SerpinB2 knockdown. Taken together, these results suggested that the TNF alpha-mediated upregulation of SerpinE1 and SerpinB2, through activation of the Erk1/2 pathway plays a crucial role in LPS-stimulated GC proliferation, and the increase in GC MMP may synergistically influence this process.

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