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Sertoli cell survival and barrier function are regulated by miR-181c/d-Pafah1b1 axis during mammalian spermatogenesis

文献类型： 外文期刊

作者： Feng, Yue 1 ; Chen, Dake 1 ; Wang, Tiansu 1 ; Zhou, Jiawei 1 ; Xu, Wenning 1 ; Xiong, Hao 1 ; Bai, Rong 1 ; Wu, Shang 1 ; Li, Jialian 1 ; Li, Fenge 1 ;

作者机构： 1.Huazhong Agr Univ, Minist Agr, Key Lab Pig Genet & Breeding, Wuhan 430070, Peoples R China

2.Huazhong Agr Univ, Minist Educ, Key Lab Agr Anim Genet Breeding & Reprod, Wuhan 430070, Peoples R China

3.Hubei Acad Agr Sci, Inst Anim Sci & Vet Med, Wuhan 430064, Peoples R China

4.Cooperat Innovat Ctr Sustainable Pig Prod, Wuhan 430070, Peoples R China

5.Huazhong Agr Univ, Coll Anim Sci & Technol, Wuhan 430070, Peoples R China

关键词： miR-181c; d; Pafah1b1; Sertoli cells; Blood-testis barrier; Ectoplasmic specialization; Tight junction; Spermatogenesis; Mammals

期刊名称：CELLULAR AND MOLECULAR LIFE SCIENCES （ 影响因子：8.0； 五年影响因子：8.7 ）

ISSN： 1420-682X

年卷期： 2022 年 79 卷 9 期

页码：

收录情况： SCI

摘要： Sertoli cells contribute to the formation of the blood-testis barrier (BTB), which is necessary for normal spermatogenesis. Recently, microRNAs (miRNAs) have emerged as posttranscriptional regulatory elements in BTB function during spermatogenesis. Our previous study has shown that miR-181c or miR-181d (miR-181c/d) is highly expressed in testes from boars at 60 days old compared with at 180 days old. Herein, we found that overexpression of miR-181c/d via miR-181c/d mimics in murine Sertoli cells (SCs) or through injecting miR-181c/d-overexpressing lentivirus in murine testes perturbs BTB function by altering BTB-associated protein distribution at the Sertoli cell-cell interface and F-actin organization, but this in vivo perturbation disappears approximately 6 weeks after the final treatment. We also found that miR-181c/d represses Sertoli cell proliferation and promotes its apoptosis. Moreover, miR-181c/d regulates Sertoli cell survival and barrier function by targeting platelet-activating factor acetylhydrolase 1b regulatory subunit 1 (Pafah1b1) gene. Furthermore, miR-181c/d suppresses PAFAH1B1 expression, reduces the complex of PAFAH1B1 with IQ motif-containing GTPase activating protein 1, and inhibits CDC42/PAK1/LIMK1/Cofilin pathway which is required for F-actin stabilization. In total, our results reveal the regulatory axis of miR-181c/d-Pafah1b1 in cell survival and barrier function of Sertoli cells and provide additional insights into miRNA functions in mammalian spermatogenesis.

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