Smoothened mediates medaka spermatogonia proliferation via Gli1-Rgcc-Cdk1 axis
Smoothened mediates medaka spermatogonia proliferation via Gli1-Rgcc-Cdk1 axis
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DOI：
10.1093/biolre/ioad090
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发表时间：
2023-11-15
影响因子：
3.6
通讯作者：
Wei，Jing
中科院分区：
文献类型：
--
作者：
Zhao，Changle;Liu，Xiang;Wei，Jing
精原细胞的增殖直接影响精子发生和男性生育能力，但其潜在的分子机制尚不清楚。在本研究中，Smoothened(Smoothened，Smo)是Hedgehog信号通路的中心转导因子，研究了Smoothened(Smoothened，Smo)在青竹中的作用，并探讨了其在精原细胞增殖中的作用及其可能机制。在体外培养的睾丸器官和青竹成熟睾丸的精原细胞系(SG3)中，Smo激活促进精原细胞增殖，而Smo抑制则诱导细胞凋亡。Smo激活后，SG3中胶质瘤相关癌基因同源1(Gli1)和细胞周期调节因子(Rgcc)的表达显著上调。此外，Gli1在转录水平上上调了Rgcc的表达，而Rgcc的过表达挽救了Smo或Gli1抑制引起的细胞凋亡。免疫共沉淀实验表明，Rgcc可与细胞周期蛋白依赖性激酶1(CDK1)相互作用，调节精原细胞的细胞周期。综上所述，我们的研究首次揭示Smo通过Gli1-Rgcc-CDK1轴介导精原细胞的增殖。此外，Smo和Gli1是精原细胞生存所必需的。本研究在分子水平上加深了对精原细胞增殖和存活的认识，为男性生育控制和生殖疾病的治疗提供了新的思路。
The proliferation of spermatogonia directly affects spermatogenesis and male fertility, but its underlying molecular mechanisms are poorly understood. In this study, Smoothened (Smo), the central transducer of Hedgehog signaling pathway, was characterized in medaka (Oryzias latipes), and its role and underlying mechanisms in the proliferation of spermatogonia were investigated.Smowas highly expressed in spermatogonia. In ex vivo testicular organ culture and a spermatogonial cell line (SG3) derived from medaka mature testis, Smo activation promoted spermatogonia proliferation, while its inhibition induced apoptosis. The expression of glioma-associated oncogene homolog 1 (gli1) and regulator of cell cycle (rgcc) was significantly upregulated in SG3 after Smo activation. Furthermore, Gli1 transcriptionally upregulated the expression ofrgcc, and Rgcc overexpression rescued cell apoptosis caused by Smo or Gli1 inhibition. Co-immunoprecipitation assay indicated that Rgcc could interact with cyclin-dependent kinase 1 (Cdk1) to regulate the cell cycle of spermatogonia. Collectively, our study firstly reveals that Smo mediates the proliferation of spermatogonia through Gli1–Rgcc–Cdk1 axis. In addition, Smo and Gli1 are necessary of the survival of spermatogonia. This study deepens our understanding of spermatogonia proliferation and survival at the molecular level, and provides insights into male fertility control and reproductive disease treatment.