College of Animal Science and Technology, Northwestern Agricultural and Forestry University, Yangling, Shaanxi, China.
Mol Cell Endocrinol. 2013 Aug 15;375(1-2):97-105. doi: 10.1016/j.mce.2013.05.017. Epub 2013 May 23.
Fibroblast growth factors (FGFs) modulate ovarian function, including FGF8 and FGF18. These FGFs activate the same receptors, although FGF18 is unusual in that it increases apoptosis in ovarian granulosa cells whereas the 'typical' response to FGF is increased proliferation. The objective of the present study was to determine which early response genes and pathways are activated by FGF8 and FGF18 in bovine granulosa cells. FGF8 increased abundance of mRNA encoding the FGF-responsive genes SPRY1, SPRY2, SPRY4, NR4A1 and NR4A3 whereas FGF18 did not. FGF8 increased but FGF18 decreased levels of mRNA encoding the growth arrest associated protein, GADD45B. FGF8 increased ERK1/2 phosphorylation but FGF18 did not. Microarray analysis identified EGR1, FOS, FOSL1, BAMBI, XIRP1 and PLK2 as other FGF8 immediate-early response genes, and FGF18 stimulated EGR1, FOSL1, BAMBI and PLK2, but not FOS or XIRP1. This study demonstrates that FGF8 and FGF18 signal through divergent pathways in ovarian granulosa cells, despite reportedly similar receptor activation patterns.
成纤维细胞生长因子(FGFs)调节卵巢功能,包括 FGF8 和 FGF18。这些 FGF 激活相同的受体,尽管 FGF18 很不寻常,因为它会增加卵巢颗粒细胞的细胞凋亡,而“典型”的 FGF 反应是增加增殖。本研究的目的是确定 FGF8 和 FGF18 在牛颗粒细胞中激活哪些早期反应基因和途径。FGF8 增加了编码 FGF 反应基因 SPRY1、SPRY2、SPRY4、NR4A1 和 NR4A3 的 mRNA 丰度,而 FGF18 则没有。FGF8 增加但 FGF18 减少与生长抑制相关的蛋白质 GADD45B 的 mRNA 水平。FGF8 增加 ERK1/2 磷酸化,但 FGF18 没有。微阵列分析确定 EGR1、FOS、FOSL1、BAMBI、XIRP1 和 PLK2 为其他 FGF8 即刻早期反应基因,而 FGF18 刺激 EGR1、FOSL1、BAMBI 和 PLK2,但不刺激 FOS 或 XIRP1。本研究表明,尽管报道的受体激活模式相似,但 FGF8 和 FGF18 在卵巢颗粒细胞中通过不同的途径信号传递。