期刊
ANIMAL REPRODUCTION SCIENCE
卷 125, 期 1-4, 页码 42-48出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.anireprosci.2011.03.002
关键词
PI3K; mTOR; HIF-1 alpha; VEGF; Letual cells
资金
- Anhui Natural Science Research Foundation [05023119, 2008AA101003]
- Ministry of Education of China [200803071048]
We recently reported that HIF-1 alpha plays a critical role in the regulation of vascular endothelial growth factor (VEGF) expression in the developing letual cells (LCs) and VEGF-dependent angiogenesis is essential for normal luteal development. Although it is believed that hypoxia is the primary inducer of VEGF, recent reports have also shown that human chorionic gonadotrophin (hCG) up-regulates VEGF expression in developing corpus luteum (CL). Therefore the present study was designed to test the induced effects of hCG on the expression of VEGF and HIF-1 alpha in LCs under normoxic and hypoxic conditions. In addition, we also investigated whether the signaling pathways such as phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK) are involved in hCG-induced VEGF in LCs. A significant increase of VEGF mRNA was found in LCs treated with hCG, which was consistent with the changes of HIFI 1 alpha protein, even under hypoxic conditions. However, there was no obvious changes of HIF-1 alpha mRNA in hCG-treated LCs between normoxic and hypoxic conditions, indicating hCG induces VEGF expression by increasing transcription of HIF-1 alpha, while hypoxia mainly increases HIF-1 alpha protein stability. When LCs were pretreated with inhibitors, we found that the PI3K/mTOR signaling pathway is required for HIF-1 alpha and VEGF expression induced by hCG, while the MAPK pathway is not required. Together, these results suggest that activation of IP3K/mTOR signaling pathway contributes to the induction of VEGF and HIF-1 alpha in hCG-treated LCs. To our knowledge this will provide a new insight into the important mechanism of hCG/LH-induced VEGF-dependent angiogenesis in the bovine ovary. (C) 2011 Elsevier B.V. All rights reserved.
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