Brain-derived neurotrophic factor promotes proliferation and progesterone synthesis in bovine granulosa cells
Brain-derived neurotrophic factor promotes proliferation and progesterone synthesis in bovine granulosa cells
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脑源性神经营养因子促进牛颗粒细胞增殖和孕酮合成
DOI：
10.1002/jcp.27536
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发表时间：
2019-06-01
影响因子：
5.6
通讯作者：
Zhou, Xu
中科院分区：
文献类型：
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作者：
Chen, Shuxiong;Wang, Fengge;Zhou, Xu
脑源性神经营养因子（BDNF）通过其受体酪氨酸激酶受体B（Trk B）参与调节卵泡的生长、卵母细胞的成熟和早期胚胎的发育。然而，目前还不清楚BDNF如何影响牛颗粒细胞（GC）的增殖和类固醇合成。在本文中，我们证实了BDNF和TrkB在牛GCs中表达，并且通过敲低BDNF或抑制TrkB来降低牛GCs的增殖和类固醇合成。对于GC增殖，BDNF增强细胞活力和S期细胞的百分比。BDNF还激活蛋白激酶B（PKB，也称为AKT）和细胞外信号调节蛋白激酶1/2（ERK 1/2）信号通路。通过AKT信号通路，BDNF增加了增殖相关基因的表达，包括细胞周期蛋白A1（CCNA 1），细胞周期蛋白E2（CCNE 2），细胞周期蛋白D1（CCND 1）和细胞周期蛋白依赖性激酶1（CDK 1）。然而，通过ERK 1/2信号通路，BDNF仅增加CCNA 1和CCNE 2的表达。关于牛GC的类固醇生成，BDNF促进孕酮（P-4）合成，但对雌二醇没有影响;它还激活AKT信号通路，并增加类固醇生成相关基因的表达，包括类固醇生成急性调节蛋白（星星）和羟基-δ-5-类固醇脱氢酶，3 β-和类固醇δ-异构酶1（HSD 3B 1）。总之，我们的数据首次表明BDNF通过TrkB-AKT和ERK 1/2信号通路促进牛GCs的增殖，并通过TrkB-AKT信号通路增加牛GCs的P-4合成。
Brain-derived neurotrophic factor (BDNF) is involved in regulating the growth of ovarian follicles, maturation of the oocyte, and development of the early embryo through its receptor, tyrosine kinase receptor B (TrkB). However, it is still unclear as to how BDNF influences proliferation and steroidogenesis of bovine granulosa cells (GCs). In this paper, we confirmed that BDNF and TrkB were expressed in bovine GCs, and that proliferation and steroidogenesis by bovine GCs were reduced by knockdown of BDNF or inhibition of TrkB. With respect to GC proliferation, BDNF enhanced cellular viability and the percentage of cells in the S phase. BDNF also activated both protein kinase B (PKB, also known as AKT) and the extracellular signal-regulated protein kinase 1/2 (ERK1/2)-signaling pathway. Through the AKT-signaling pathway, BDNF increased the expression of proliferation-related genes, including cyclin A1 (CCNA1), cyclin E2 (CCNE2), cyclin D1 (CCND1), and cyclin-dependent kinase 1 (CDK1). However, through the ERK1/2 signaling pathway, BDNF only increased the expression of CCNA1 and CCNE2. Regarding steroidogenesis by bovine GCs, BDNF promoted progesterone (P-4) synthesis, but had no effect on estradiol; it also activated the AKT-signaling pathway and increased the expression of steroidogenesis-related genes, including steroidogenic acute regulatory protein (STAR) and hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 (HSD3B1). In summary, our data are the first to show that BDNF promotes the proliferation of bovine GCs through TrkB-AKT and ERK1/2 signaling pathways and increases P-4 synthesis by bovine GCs through the TrkB-AKT signaling pathway.