Key Laboratory of Stem Cell Engineering and Regenerative Medicine of Fujian Province University, Fujian Medical University, Fuzhou, P. R. China.
Department of Anatomy, Histology, and Embryology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, P. R. China.
Andrology. 2021 Nov;9(6):1923-1933. doi: 10.1111/andr.13072. Epub 2021 Jul 10.
The tricho-rhino-phalangeal syndrome-1 gene (Trps1) is an atypical GATA family member. Although current studies of Trps1 mainly focus on tumors, whether Trps1 plays a role in the male reproductive system remains unknown.
The purpose of this study was to elucidate the function of Trps1 in Leydig cells, indicating its regulatory mechanism on the cell cycle.
Gene-silencing technology, RNA-seq, RT-qPCR, and western blotting were used to evaluate the function of Trps1 in mouse primary Leydig cells and MLTC-1 cells. In addition, ChIP-base sets and ChIP-qPCR were employed to further assess the regulatory mechanism of Trps1 in MLTC-1 cells.
Knockdown of Trps1 in Leydig cells significantly suppressed phosphorylation of Src and Akt and expression of Ccnd1, which was accompanied by impairment of cell proliferative ability. Trps1 may affect the cell cycle through the Src/Akt/Ccnd1 signaling pathway. In addition, Trps1 may bind to the promoter of Srcin1 to regulate its transcription, thus influencing Src phosphorylation levels and the proliferation of Leydig cells.
Src increases in Leydig cells during pubertal development, suggesting its functional involvement in differentiated adult Leydig cells. Inhibition of the Src/Akt pathway would reduce Ccnd1 expression. In the present study, we found that Trps1 may regulate the phosphorylation level of Src and Akt through Srcin1, targeting Ccnd1 to influence mouse Leydig cell proliferation. These findings shed light on the regulation of Trps1 on cell proliferation and differentiation of mouse Leydig cells.
三指-鼻-唇综合征 1 型基因（Trps1）是一种非典型的 GATA 家族成员。尽管目前对 Trps1 的研究主要集中在肿瘤上，但 Trps1 是否在男性生殖系统中发挥作用尚不清楚。
本研究旨在阐明 Trps1 在 Leydig 细胞中的功能，表明其对细胞周期的调节机制。
采用基因沉默技术、RNA-seq、RT-qPCR 和 Western blot 等方法，评估 Trps1 在小鼠原代 Leydig 细胞和 MLTC-1 细胞中的功能。此外，还采用 ChIP-base 试剂盒和 ChIP-qPCR 进一步评估 Trps1 在 MLTC-1 细胞中的调控机制。
在 Leydig 细胞中敲低 Trps1 可显著抑制 Src 和 Akt 的磷酸化以及 Ccnd1 的表达，同时损害细胞增殖能力。Trps1 可能通过 Src/Akt/Ccnd1 信号通路影响细胞周期。此外，Trps1 可能与 Srcin1 的启动子结合，调节其转录，从而影响 Src 的磷酸化水平和 Leydig 细胞的增殖。
Src 在青春期发育过程中在 Leydig 细胞中增加，表明其在分化的成年 Leydig 细胞中具有功能作用。Src/Akt 通路的抑制会降低 Ccnd1 的表达。在本研究中，我们发现 Trps1 可能通过 Srcin1 调节 Src 和 Akt 的磷酸化水平，靶向 Ccnd1 影响小鼠 Leydig 细胞增殖。这些发现揭示了 Trps1 对小鼠 Leydig 细胞增殖和分化的调节作用。
