S100A4靶向PPP1CA/IL-17以抑制绵羊子宫内膜上皮细胞衰老。
S100A4 targets PPP1CA/IL-17 to inhibit the senescence of sheep endometrial epithelial cells.
作者信息
Jiao Xiyao, Jiao Yaoxuan, Cui Jingwen, Zhang Haorui, Li Xiangyun, Chu Zhili, Wu Xinglong
机构信息
College of Animal Science and Technology, Hebei Technology Innovation Center of Cattle and Sheep Embryo, Hebei Agricultural University, Baoding, China.
School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.
出版信息
Front Vet Sci. 2024 Nov 27;11:1466482. doi: 10.3389/fvets.2024.1466482. eCollection 2024.
BACKGROUND
Gonadotropin-releasing hormone (GnRH) is commonly used in animal reproduction and production, but it was previously reported that GnRH decreases the embryo implantation rate during artificial insemination or embryo transfer in sheep. In addition to the finding that GnRH can target S100A4 to inhibit endometrial epithelial cells proliferation, it was also found that endometrial cells were in poor condition and experienced cell death in S100A4 knockout mice, but the mechanism is unclear.
METHODS
The protein PPP1CA, which interacts with S100A4, was detected by immunoprecipitation-mass spectrometry of overexpression and knockdown of S100A4 and PPP1CA. The effect of S100A4 and PPP1CA on cell senescence was detected by Galactosidase staining. To further reveal the mechanism effect of S100A4 and PPP1CA on cell senescence, transcriptome sequencing was conducted. Additionally, experiments were performed to assess PPP1CA protein expression in the endometrial tissue of S100A4 knockout mice.
RESULTS
S100A4 inhibited cell senescence by activating PPP1CA, while PPP1CA overexpression suppressed the activation of the IL-17 signaling pathway. Inhibition of the IL-17 signaling pathway inhibited the senescence of endometrial cells.
CONCLUSION
S100A4 can target the PPP1CA/IL-17 signaling pathway and inhibit endometrial epithelial cell senescence.
背景
促性腺激素释放激素（GnRH）常用于动物繁殖和生产，但先前有报道称，GnRH会降低绵羊人工授精或胚胎移植期间的胚胎着床率。除了发现GnRH可靶向S100A4以抑制子宫内膜上皮细胞增殖外，还发现在S100A4基因敲除小鼠中，子宫内膜细胞状态不佳且发生细胞死亡，但其机制尚不清楚。
方法
通过对S100A4和PPP1CA进行过表达和敲低的免疫沉淀-质谱法检测与S100A4相互作用的蛋白质PPP1CA。通过半乳糖苷酶染色检测S100A4和PPP1CA对细胞衰老的影响。为进一步揭示S100A4和PPP1CA对细胞衰老的机制作用，进行了转录组测序。此外，还进行了实验以评估S100A4基因敲除小鼠子宫内膜组织中PPP1CA蛋白的表达。
结果
S100A4通过激活PPP1CA抑制细胞衰老，而PPP1CA的过表达抑制了IL-17信号通路的激活。抑制IL-17信号通路可抑制子宫内膜细胞的衰老。
结论
S100A4可靶向PPP1CA/IL-17信号通路并抑制子宫内膜上皮细胞衰老。
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