Regulation of the early growth response-1 binding protein NAB2 in bovine granulosa cells and effect on connective tissue growth factor expression

Ovarian fibrosis is associated with increased expression of the transcription factor, Early growth response-1 (EGR1) and connective tissue growth factor (CCN2) in granulosa cells. The transcriptional activity of EGR1 is under negative feedback control by NAB1 and NAB2, but little is known about NAB expression in granulosa cells. Using a well-defined bovine in-vitro granulosa cell model, we show that NAB2 but not NAB1 mRNA is upregulated by fibroblast growth factor (FGF)1 and FGF2, but not by FGF4 or FGF8b. Overexpressing NAB2 abrogated the ability of FGF8b to increase EGR1 and CCN2 mRNA, as well as mRNAs encoding other FGF-target genes. Surprisingly, overexpression of NAB2 in the absence of growth factor stimulation increased abundance of mRNA encoding CCN2 and EGR1, and decreased estradiol secretion. We conclude that NAB2 is expressed in granulosa cells and plays a role in regulating EGR1-induced CCN2 expression, although cross-talk with other signaling pathways is likely occurring.