Cooperative regulation of Gja1 expression by members of the AP-1 family cJun and cFos in TM3 Leydig and TM4 Sertoli cells
Cooperative regulation of Gja1 expression by members of the AP-1 family cJun and cFos in TM3 Leydig and TM4 Sertoli cells
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DOI：
10.1016/j.gene.2017.09.017
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发表时间：
2017-11-30
期刊：
影响因子：
3.5
通讯作者：
Martin, Luc J.
中科院分区：
文献类型：
--
作者：
Ghouili, Firas;Martin, Luc J.
在睾丸内，由Gja 1编码的连接蛋白43在间质细胞之间以及支持细胞和精原细胞之间的细胞间通讯中起重要作用。在成年男性中，间质细胞是维持精子发生的睾酮的主要生产者，而支持细胞滋养、保护和支持分化的生殖细胞。先前已经表明AP-1家族的成员调节子宫肌层细胞中的Gja 1表达，这表明这种调节机制也可能与睾丸内相关。因此，我们在TM 3 Leydig和TM 4 Sertoli细胞内进行了AP-1表达质粒与不同小鼠Gja 1启动子/荧光素酶报告基因构建体的共转染。我们发现，cJun和cFos之间的功能合作激活Gja 1的表达，需要一个AP-1的DNA调控元件位于-132和-26 bp之间。此外，这种协同作用依赖于cFos募集到小鼠Gja 1启动子的该区域。因此，我们的数据表明，AP-1的成员是重要的Gja 1的最佳表达睾丸支持细胞和间质细胞。
Within the testis, connexin43 encoded by Gja1 plays an important role in cell-to-cell communication between Leydig cells as well as between Sertoli cells and spermatogonia. In the adult male, Leydig cells are the principal producers of testosterone sustaining spermatogenesis, while Sertoli cells nourish, protect and support the differentiating germ cells. It has been shown previously that members of the AP-1 family regulate Gja1 expression in myometrial cells, suggesting that such regulatory mechanism may also be relevant within the testis. Thus, we performed cotransfections of AP-1 expression plasmids with different mouse Gja1 promoter/luciferase reporter constructs within TM3 Leydig and TM4 Sertoli cells. We showed that a functional cooperation between cJun and cFos activates Gja1 expression and requires an AP-1 DNA regulatory element located between - 132 and - 26 bp. In addition, such synergy relies on the recruitment of cFos to this region of the mouse Gja1 promoter. Hence, our data indicate that AP-1 members are important for optimal expression of Gja1 within Sertoli and Leydig cells from the testis.