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Dmrt1 通过抑制 TLR4 信号通路来调节山羊雄性生殖干细胞的免疫反应。

Dmrt1 regulates the immune response by repressing the TLR4 signaling pathway in goat male germline stem cells.

机构信息

College of Veterinary Medicine, Northwest A & F University, Shaanxi Centre of Stem Cells Engineering & Technology, Yangling, Shaanxi 712100, China.

College of Life Sciences, Northwest A & F University, Yangling, Shaanxi 712100, China.

出版信息

Zool Res. 2021 Jan 18;42(1):14-27. doi: 10.24272/j.issn.2095-8137.2020.186.

DOI:10.24272/j.issn.2095-8137.2020.186
PMID:33420764
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7840460/
Abstract

Double sex and mab-3-related transcription factor 1 (Dmrt1), which is expressed in goat male germline stem cells (mGSCs) and Sertoli cells, is one of the most conserved transcription factors involved in sex determination. In this study, we highlighted the role of Dmrt1 in balancing the innate immune response in goat mGSCs. Dmrt1 recruited promyelocytic leukemia zinc finger (Plzf), also known as zinc finger and BTB domain-containing protein 16 (Zbtb16), to repress the Toll-like receptor 4 (TLR4)-dependent inflammatory signaling pathway and nuclear factor (NF)-κB. Knockdown of Dmrt1 in seminiferous tubules resulted in widespread degeneration of germ and somatic cells, while the expression of proinflammatory factors were significantly enhanced. We also demonstrated that Dmrt1 stimulated proliferation of mGSCs, but repressed apoptosis caused by the immune response. Thus, Dmrt1 is sufficient to reduce inflammation in the testes, thereby establishing the stability of spermatogenesis and the testicular microenvironment.

摘要

双性和 mab-3 相关转录因子 1（Dmrt1）在山羊精原干细胞（mGSCs）和支持细胞中表达，是参与性别决定的最保守的转录因子之一。在这项研究中，我们强调了 Dmrt1 在平衡山羊 mGSCs 固有免疫反应中的作用。Dmrt1 募集早幼粒细胞白血病锌指（Plzf），也称为锌指和 BTB 结构域蛋白 16（Zbtb16），以抑制 Toll 样受体 4（TLR4）依赖性炎症信号通路和核因子（NF）-κB。在生精小管中敲低 Dmrt1 会导致生殖细胞和体细胞广泛退化，而促炎因子的表达则显著增强。我们还表明，Dmrt1 刺激 mGSCs 的增殖，但抑制由免疫反应引起的细胞凋亡。因此，Dmrt1 足以减轻睾丸中的炎症，从而维持精子发生和睾丸微环境的稳定性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7619/7840460/ee8a89a6c74d/zr-42-1-14-7.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7619/7840460/86649ffe2d34/zr-42-1-14-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7619/7840460/56f03fc03048/zr-42-1-14-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7619/7840460/ee8a89a6c74d/zr-42-1-14-7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7619/7840460/1ad0f723415a/zr-42-1-14-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7619/7840460/0f650995c6a0/zr-42-1-14-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7619/7840460/8049c14dfbeb/zr-42-1-14-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7619/7840460/b35993bcdc96/zr-42-1-14-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7619/7840460/86649ffe2d34/zr-42-1-14-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7619/7840460/56f03fc03048/zr-42-1-14-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7619/7840460/ee8a89a6c74d/zr-42-1-14-7.jpg

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