GPER mediates the IL6/JAK2/STAT3 pathway involved in VEGF expression in swine ovary GCs

in Journal of Molecular Endocrinology
Authors:
Longfei Xiao Animal Science and Technology College, Beijing University of Agriculture, Beijing, China

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https://orcid.org/0000-0001-5790-6645
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Zihui Wang Animal Science and Technology College, Beijing University of Agriculture, Beijing, China

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Ning Lu Animal Science and Technology College, Beijing University of Agriculture, Beijing, China

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Yanan He Zhangjiagang Agriculture and Rural Affairs Bureau, Jiangsu, China

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Limin Qiao Department of Animal Husbandry and Veterinary, Beijing Vocational College of Agriculture, Beijing, China

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Xihui Sheng Animal Science and Technology College, Beijing University of Agriculture, Beijing, China

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Xiaolong Qi Animal Science and Technology College, Beijing University of Agriculture, Beijing, China

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Kai Xing Animal Science and Technology College, Beijing University of Agriculture, Beijing, China

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Yong Guo Animal Science and Technology College, Beijing University of Agriculture, Beijing, China

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Di Chang Animal Science and Technology College, Beijing University of Agriculture, Beijing, China

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Xiangguo Wang Animal Science and Technology College, Beijing University of Agriculture, Beijing, China

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Junjin Zhao National Grazing Headquarter, Beijing, China

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Xiaobin Deng Beijing Tianyuanaorui Bio-technology Limited, Beijing, China

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Hemin Ni Animal Science and Technology College, Beijing University of Agriculture, Beijing, China

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Jian Kang Guangdong Polytechnic of Science and Trade, Guangdong, China

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Correspondence should be addressed to X Wang or H Ni: xiangguo731@bua.edu.cn or nihemin@aliyun.com
DOI:
https://doi.org/10.1530/JME-21-0125
Volume/Issue:
Volume 68: Issue 1
Article Type:
Research Article
Page Range:
23–33
Online Publication Date:
12 Nov 2021
Copyright:
© Society for Endocrinology 2021
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Vascular endothelial growth factor (VEGF) plays a pivotal role in angiogenesis in ovaries, particularly during follicular development and ovulation. Interleukin-6 (IL-6) is one of the major pro-inflammatory factors that are involved in the angiogenesis process physiologically and pathologically. Previous studies have shown that 17β-estradiol (E2) stimulates VEGF expression by upregulating hypoxia-inducible factor 1α (HIF-1α) in many cell types, and the high level of E2 causes an inflammatory-like microenvironment before ovulation. However, whether IL-6 signaling is involved in E2-regulating VEGF expression in swine granulosa cells (GCs) is still unknown. In this study, we found the estrogen membrane receptor, G-protein-coupled estrogen receptor 1 (GPER), was expressed in swine GCs, and the expression level of GPER, HIF-1α, and VEGF increased with follicular development. In vitro study showed that E2, ICI182780, and GPER agonist (G1) promoted the expressions of HIF-1α and VEGF in swine GCs, while GPER antagonist (G15) inhibited the stimulating effect of E2 and G1. Meanwhile, G15 inhibited the stimulating effect of E2 and G1 on IL-6 mRNA expression and secretion. Furthermore, IL-6 antibody and AG490 (JAK2/STAT3 inhibitor) attenuated G1-induced HIF-1α and VEGF expression. In conclusion, this study revealed how estrogen-induced HIF-1α and VEGF expressions in swine GCs are mediated through GPER-derived IL-6 secretion leading to JAK2/STAT3 activation.

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Online ISSN:
1479-6813
Print ISSN:
0952-5041
Copyright:
© Society for Endocrinology 2021
Page(s):
11
Article Type:
Research Article
Received Date:
18 Oct 2021
Accepted Date:
22 Oct 2021
Print Publication Date:
01 Jan 2022
Online Publication Date:
12 Nov 2021
Keywords:
GPER; IL-6; JAK2/STAT3 pathway; VEGF

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