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ORIGINAL RESEARCH article

Front. Vet. Sci.
Sec. Animal Reproduction - Theriogenology
Volume 11 - 2024 | doi: 10.3389/fvets.2024.1466482
This article is part of the Research Topic Reproductive biotechnologies and challenges in their application View all 17 articles

S100A4 targets PPP1CA/IL-17 to promote the senescence of sheep endometrial epithelial cells

Provisionally accepted
Xiyao Jiao Xiyao Jiao 1Yaoxuan Jiao Yaoxuan Jiao 1*Jingwen Cui Jingwen Cui 2*Haorui Zhang Haorui Zhang 2*Xiangyun Li Xiangyun Li 1*Zhili Chu Zhili Chu 2,3*Xinglong Wu Xinglong Wu 1*
  • 1 1. College of Animal Science and Technology, Hebei Technology Innovation Center of Cattle and Sheep Embryo, Hebei Agricultural University, Baoding, China
  • 2 School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan Province, China
  • 3 International Joint Research Laboratory for Recombinant Pharmaceutical Protein Expression System of Henan, Xinxiang Medical University, Xinxiang, Henan Province, China

The final, formatted version of the article will be published soon.

    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 cell 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, and galactosidase staining revealed that overexpression of S100A4 and PPP1CA inhibited cell senescence. Transcriptome sequencing revealed that both S100A4 and PPP1CA targeted and regulated the IL-17 signaling pathway. In vivo experiments confirmed that PPP1CA protein was expressed in the endometria of mice with S100A4 knockout. 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 improved the senescence of endometrial cells. Conclusion: Knockdown of S100A4 can target the PPP1CA/IL-17 signaling pathway and promote endometrial cell senescence.

    Keywords: cell senescence, GnRH, S100A4, PPP1CA, IL-17

    Received: 18 Jul 2024; Accepted: 06 Nov 2024.

    Copyright: © 2024 Jiao, Jiao, Cui, Zhang, Li, Chu and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Yaoxuan Jiao, 1. College of Animal Science and Technology, Hebei Technology Innovation Center of Cattle and Sheep Embryo, Hebei Agricultural University, Baoding, China
    Jingwen Cui, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, Henan Province, China
    Haorui Zhang, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, Henan Province, China
    Xiangyun Li, 1. College of Animal Science and Technology, Hebei Technology Innovation Center of Cattle and Sheep Embryo, Hebei Agricultural University, Baoding, China
    Zhili Chu, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, Henan Province, China
    Xinglong Wu, 1. College of Animal Science and Technology, Hebei Technology Innovation Center of Cattle and Sheep Embryo, Hebei Agricultural University, Baoding, China

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