Summary: | In female mammals, the abnormal apoptosis of ovarian granulosa cells (GCs) impairs follicular development and causes reproductive dysfunction. Many studies have indicated that the <i>FGFR1</i> 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 <i>FGFR1</i>, as well as the biological effects of <i>p65</i> and <i>FGFR1</i> on the survival of GCs and follicular development. In porcine follicles and GCs, we found that <i>p65</i> and <i>FGFR1</i> were exclusively expressed in the GCs of follicles, and the mRNA and protein levels of <i>p65</i> and <i>FGFR1</i> significantly increased from small to large follicles. Both <i>p65</i> and <i>FGFR1</i> were found to activate the PI3K signaling pathway, and the expressions of proliferation markers (<i>PCNA</i> and <i>MKI67</i>) and the anti-apoptotic gene <i>BCL2</i> were significantly increased by <i>p65</i> and <i>FGFR1</i>. Furthermore, both <i>p65</i> and <i>FGFR1</i> 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 <i>FGFR1</i> to positively regulate its transcription. Moreover, p65 was further found to enhance the pro-proliferation and anti-apoptotic effects of <i>FGFR1</i>. Taken together, p65 may target the −348/−338 region of <i>FGFR1</i>, promote the transcription of <i>FGFR1</i>, and enhance the pro-proliferation effect and anti-apoptotic effect of <i>FGFR1</i> 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.
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