H19 regulates the proliferation of bovine male germline stem cells via IGF-1 signaling pathway
H19 regulates the proliferation of bovine male germline stem cells via IGF-1 signaling pathway
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DOI：
10.1002/jcp.26920
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发表时间：
2019-01-01
影响因子：
5.6
通讯作者：
Hua, Jinlian
中科院分区：
文献类型：
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作者：
Lei, Qijing;Pan, Qin;Hua, Jinlian
雄性生殖干细胞（mGSC）的自我更新和分化为持续的精子发生提供了基本功能。生殖干细胞体外培养研究对于基础生物学研究和实际应用具有重要意义。 GDNF、bFGF、CSF1 和 EGF 等生长因子可以维持 mGSC 的自我更新。胰岛素样生长因子1（IGF-1）是一种重要的生长因子，据报道其途径可维持多种类型干细胞的存活，并在男性生殖中发挥重要作用。然而，IGF-1途径调节mGSC自我更新的机制仍不清楚。我们分析了IGF-1对牛mGSC增殖和凋亡的影响。我们评估了牛和小鼠组织中长非编码 RNA (LncRNA) H19 的表达谱。此外，我们研究了 LncRNA H19 是否可以调节 IGF-1 通路。结果表明，IGF-1能够激活AKT和ERK信号通路的磷酸化，IGF-1通路在调节牛mGSC的增殖和凋亡中发挥重要作用。当使用IGF-1R特异性抑制剂（鬼臼苦素）阻断IGF-1受体（IGF-1R）时，mGSC的增殖率降低，而mGSC的凋亡率增加。 LncRNA H19 可以调节 IGF-1 信号通路，从而调节 mGSC 的增殖和凋亡。当通过注射含有病毒的上清液干扰H19时，生精小管中的细胞数量减少。因此，LncRNA H19通过IGF-1信号通路参与mGSC增殖和凋亡的调节。
Self-renewal and differentiation of male germline stem cells (mGSCs) provide the basic function for continual spermatogenesis. Studies of in vitro culture of germline stem cells are important and meaningful for basic biological research and practical application. Growth factors, such as GDNF, bFGF, CSF1, and EGF, could maintain the self-renewal of mGSCs. Insulin-like growth factor 1 (IGF-1), an important growth factor, and its pathway have been reported to maintain the survival of several types of stem cells and play important roles in male reproduction. However, the mechanism through which the IGF-1 pathway acts to regulate the self-renewal of mGSCs remains unclear. We analyzed the effect of IGF-1 on the proliferation and apoptosis of bovine mGSCs. We evaluated the expression profile of long noncoding RNA (LncRNA) H19 in bovine and mouse tissues. Moreover, we investigated whether LncRNA H19 could regulate the IGF-1 pathway. Results showed that IGF-1 could activate the phosphorylation of AKT and ERK signaling pathways, and the IGF-1 pathway played an important role in regulating the proliferation and apoptosis of bovine mGSCs. The proliferation rate of mGSCs decreased, whereas the apoptosis rate of mGSCs increased when the IGF-1 receptor (IGF-1R) was blocked using the IGF-1R-specific inhibitor (picropodophyllin). LncRNA H19 could regulate the IGF-1 signaling pathway and, consequently, the proliferation and apoptosis of mGSCs. The number of cells in the seminiferous tubule decreased when H19 was interfered by injecting a virus-containing supernatant. Hence, LncRNA H19 participated in the regulation of the proliferation and apoptosis of mGSCs via the IGF-1 signaling pathway.