P65 Targets FGFR1 to Regulate the Survival of Ovarian Granulosa Cells.

In female mammals, the abnormal apoptosis of ovarian granulosa cells (GCs) impairs follicular development and causes reproductive dysfunction. Many studies have indicated that the gene of the PI3K signaling pathway and the p65 subunit of the transcription factor NF-κB may regulate the proliferation and apoptosis of GCs involved in follicular development. However, little is known about whether p65 regulates the transcription of , as well as the biological effects of and on the survival of GCs and follicular development. In porcine follicles and GCs, we found that and were exclusively expressed in the GCs of follicles, and the mRNA and protein levels of and significantly increased from small to large follicles. Both and were found to activate the PI3K signaling pathway, and the expressions of proliferation markers ( and ) and the anti-apoptotic gene were significantly increased by and . Furthermore, both and were observed to promote cell proliferation and inhibit the cell apoptosis of GCs, and p65 was confirmed to bind at the -348/-338 region of to positively regulate its transcription. Moreover, p65 was further found to enhance the pro-proliferation and anti-apoptotic effects of . Taken together, p65 may target the -348/-338 region of , promote the transcription of , and enhance the pro-proliferation effect and anti-apoptotic effect of to facilitate the growth of follicles. This study will provide useful information for further investigations on the p65-mediated-FGFR1 signaling pathway during folliculogenesis in mammals.