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表皮生长因子受体通过丝裂原活化蛋白激酶/细胞外信号调节激酶(ERK)信号通路促进鹌鹑卵泡颗粒细胞的增殖。

EGFR promotes the proliferation of quail follicular granulosa cells through the MAPK/extracellular signal-regulated kinase (ERK) signaling pathway.

机构信息

Institute of Animal Husbandry and Veterinary, Hubei Academy of Agricultural Science , Wuhan , China.

Key Laboratory of Animal Embryo Engineering and Molecular Breeding of Hubei Province , Wuhan , China.

出版信息

Cell Cycle. 2019 Oct;18(20):2742-2756. doi: 10.1080/15384101.2019.1656952. Epub 2019 Aug 29.

Abstract

Follicles develop into preovulatory follicles during folliculogenesis and the majority of small yellow follicles become atretic and gets reabsorbed. In this study, based the RNA-seq results of duck ovary, epidermal growth factor receptor (EGFR) was selected as a candidate gene in follicular development and the role was explored. The results demonstrated that EGFR-P8 was the quail EGFR core promoter. It had an E2F4 binding site within EGFR core promoter. E2F4 overexpression significantly increased EGFR expression in quail granulosa cells (GCs). However, the effect was abolished when the GCs were treated with corynoxeine, an inhibitor of the mitogen-activated protein kinase/extracellular regulated protein kinase (MAPK/ERK) signaling pathway. Moreover, luciferase reporter assay and chromatin immunoprecipitation experiments showed that E2F4 upregulated the expression of EGFR expression, which increased E2 and P4 production. In addition, EGFR regulated GCs proliferation and affected follicular development. Taken together, our findings suggested that EGFR, which was regulated by E2F4, enhanced the expression of MAPK/ERK pathway components and follicular development. These results provided an important basis for an improved understanding of the MAPK/ERK pathway and new insight into the development of quail follicles.

摘要

在卵泡发生过程中,卵泡发育成排卵前卵泡,大多数小黄卵泡发生闭锁并被重新吸收。本研究基于鸭卵巢的 RNA-seq 结果,选择表皮生长因子受体 (EGFR) 作为卵泡发育的候选基因,并探讨其作用。结果表明,EGFR-P8 是鹌鹑 EGFR 核心启动子。它在 EGFR 核心启动子内有一个 E2F4 结合位点。E2F4 的过表达显著增加了鹌鹑颗粒细胞 (GCs) 中 EGFR 的表达。然而,当 GCs 用 corynoxeine 处理时,这种作用被消除,corynoxeine 是丝裂原激活的蛋白激酶/细胞外调节蛋白激酶 (MAPK/ERK) 信号通路的抑制剂。此外,荧光素酶报告基因检测和染色质免疫沉淀实验表明,E2F4 上调了 EGFR 的表达,从而增加了 E2 和 P4 的产生。此外,EGFR 调节 GCs 的增殖并影响卵泡发育。综上所述,我们的研究结果表明,EGFR 受 E2F4 调控,增强了 MAPK/ERK 通路成分的表达和卵泡发育。这些结果为进一步了解 MAPK/ERK 通路提供了重要依据,并为鹌鹑卵泡发育提供了新的见解。

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