Sertoli cell-derived exosome-mediated transfer of miR-145-5p inhibits Leydig cell steroidogenesis by targeting steroidogenic factor 1
Sertoli cell-derived exosome-mediated transfer of miR-145-5p inhibits Leydig cell steroidogenesis by targeting steroidogenic factor 1
复制标题
支持细胞衍生的外泌体介导的 miR-145-5p 转移通过靶向类固醇生成因子 1 抑制 Leydig 细胞类固醇生成
DOI：
10.1096/fj.202002589rrrr
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发表时间：
2021-06-01
期刊：
影响因子：
4.8
通讯作者：
Huang, Yadong
中科院分区：
文献类型：
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作者：
Liang, Jinlian;Li, Hanhao;Huang, Yadong
在哺乳动物睾丸中，支持细胞（Sertoli cells，SC）分为未成熟支持细胞（immature SCs，ISCs）和成熟支持细胞（adult SCs，ASCs），它们在调节睾丸间质细胞的发育和功能方面起着重要作用。然而，不同SC类型对Leydig细胞功能的影响知之甚少。在此，我们的研究表明miR-145- 5 p在不同阶段的SC中的表达显著不同，在ISCs中观察到最高表达。外泌体介导miR-145- 5 p从ISCs转移到Leydig细胞。在Leydig细胞中过表达miR-145- 5 p显著下调类固醇生成基因的表达并抑制睾酮合成。此外，miR-145- 5 p通过直接靶向类固醇生成因子-1（Sf-1）发挥作用并下调SF-1的表达，SF-1进一步下调类固醇生成基因的表达，诱导脂滴积聚，并最终抑制睾酮产生。这些发现表明SC衍生的miR-145- 5 p在调节Leydig细胞的功能中起重要作用，因此可以作为青春期男性性腺功能减退症发育异常的诊断生物标志物。
In the mammalian testis, two distinct populations of Sertoli cells (SCs), the immature SCs (ISCs) and adult SCs (ASCs), play significant roles in regulating the development and function of Leydig cells. However, the effect of different SC types on the function of Leydig cells is poorly understood. Here, our study showed that miR-145-5p expression was significantly different in SCs at different stages, with the highest expression observed in ISCs. Exosomes mediate the transfer of miR-145-5p from ISCs to Leydig cells. Overexpression of miR-145-5p in Leydig cells significantly downregulated steroidogenic gene expression and inhibited testosterone synthesis. Additionally, miR-145-5p functioned by directly targeted steroidogenic factor-1 (Sf-1) and downregulated the expression of SF-1, which further downregulated the expression of steroidogenic genes, induced accumulation of lipid droplets, and eventually suppressed testosterone production. These findings demonstrate that SC-derived miR-145-5p plays a significant role in regulating the functions of Leydig cells and may therefore serve as a diagnostic biomarker for male hypogonadism developmental abnormalities during puberty.