Common and distinct factors regulate expression of mRNA for ETV5 and GDNF, Sertoli cell proteins essential for spermatogonial stem cell maintenance
Common and distinct factors regulate expression of mRNA for ETV5 and GDNF, Sertoli cell proteins essential for spermatogonial stem cell maintenance
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DOI：
10.1016/j.yexcr.2007.05.002
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发表时间：
2007-08-15
影响因子：
3.7
通讯作者：
Cooke, Paul S.
中科院分区：
文献类型：
--
作者：
Simon, Liz;Ekman, Gail C.;Cooke, Paul S.
Ets变异基因5 （ETVS）和胶质细胞源性神经营养因子（GDNF）在支持细胞中产生，是小鼠精原干细胞（ssc）维持和自我更新所必需的。据报道，成纤维细胞生长因子（FGFs）刺激Etv5 mRNA表达，FSH在支持细胞培养中刺激Gdnf mRNA表达，但没有其他关于调节干细胞维持所必需的这些关键支持细胞蛋白的因子的信息。在本研究中，我们利用TM4小鼠支持细胞系研究了ETV5和GDNF的调控。FGF2刺激了Etv5 mRNA表达的时间和剂量依赖性增加，在25 ng/ml FGF2处理后6小时最大增加8.3倍。FGF2对Etv5和Gdnf mRNA的影响部分是通过丝裂原活化蛋白激酶（MAPK）和磷脂酰肌醇3-激酶（PI3K）信号级联介导的。在fgf2处理的细胞中，MAPK （PD98059）和PI3K （wortmannin）通路的特异性抑制剂降低了Etv5和Gdnf mRNA的表达。表皮生长因子（EGF）刺激Etv5 mRNA表达，但对Gdnf mRNA表达无刺激作用。TNF α和IL-1 β刺激Gdnf mRNA，但对Etv5 mRNA无影响。支持细胞的其他激素调节因子如睾酮、三碘甲状腺原氨酸和激活素A不影响Etv5或Gdnf mRNA的表达。原代Sertoli细胞培养的结果证实了TM4细胞系的发现，验证了TM4模型对Etv5和Gdnf mRNA表达的调节作用。总之，我们已经确定了Sertoli细胞中调节Etv5和Gdnf mRNA的共同和独特途径，FGFs正在成为控制ssc的Sertoli细胞蛋白的关键调节器。(c) 2007爱思唯尔公司版权所有。
Ets variant gene 5 (ETVS) and glial cell-derived neurotrophic factor (GDNF) are produced in Sertoli cells and required for maintenance and self-renewal of spermatogonial stem cells (SSCs) in mice. Fibroblast growth factors (FGFs) have been reported to stimulate Etv5 mRNA expression, and FSH was shown to stimulate Gdnf mRNA in Sertoli cell cultures, but there is no other information on factors that regulate these key Sertoli cell proteins necessary for stem cell maintenance. In this study, we investigated regulation of ETV5 and GDNF using the TM4 murine Sertoli cell line. FGF2 stimulated a time- and dose-dependent increase in Etv5 mRNA expression, with a maximal 8.3-fold increase at 6 h following 25 ng/ml FGF2 treatment. This FGF2 dose also stimulated Gdnf mRNA at 48 h. FGF2 effects on Etv5 and Gdnf mRNA were partially mediated through mitogen-activated protein kinase (MAPK) and phosphatidyl mositol 3-kinase (PI3K)-signaling cascades. Specific inhibitors of MAPK (PD98059) and PI3K (wortmannin) pathways reduced Etv5 and Gdnf mRNA expression in FGF2-treated cells. Epidermal growth factor (EGF) stimulated Etv5 mRNA but not Gdnf mRNA. TNF alpha and IL-1 beta stimulated Gdnf mRNA, but had no effect on Etv5 mRNA. Other hormonal regulators of Sertoli cells such as testosterone, triiodothyronine and activin A did not affect Etv5 or Gdnf mRNA expression. Results with primary Sertoli cell cultures confirmed findings obtained with the TM4 cell line, validating the use of the TM4 model to examine regulation of Etv5 and Gdnf mRNA expression. In conclusion, we have identified common and unique pathways that regulate Etv5 and Gdnf mRNA in Sertoli cells, and FGFs are emerging as key regulators of the Sertoli cell proteins that control SSCs. (c) 2007 Elsevier Inc. All rights reserved.