STAT4 targets KISS1 to promote the apoptosis of ovarian granulosa cells.

Journal of Ovarian Research
Yao JiangXiaolong Yuan

Abstract

In mammals, it is known that the estradiol-17β (E2) is mainly synthetized in ovarian granulosa cells (GCs), and the excessive apoptosis of GCs induces the follicular atresia. Many studies have implicated the essential role of KISS1, with the pro-synthetic effect of E2 and the anti-apoptotic effect on GCs, in the mammalian folliculogenesis, and several STAT4 potential binding sites were previously predicted on the promoter of KISS1 in pigs. However, the biological effects of STAT4 on GCs and the molecular regulation between STAT4 and KISS1 remained largely unknown. Using the porcine GCs as the cellular model, the overexpression plasmid, small interfering RNA, 5'-deletion and luciferase assay were applied to investigate the molecular mechanisms for STAT4 regulating the expression of KISS1. In this study, the STAT4 negatively regulated the mRNA and protein levels of KISS1 in porcine GCs, and the mRNA level of STAT4 was observed to significantly decrease from immature to mature follicles, which was inversed with that of KISS1. The relative luciferase activity of KISS1 promoter was significantly increased with deletion of the fourth potential binding site (- 305/- 295), and ChIP further confirmed that the STAT4 bound at - 305/- 295 ...Continue Reading

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Methods Mentioned

BETA
KISS
PCR
flow cytometry
ChIP

Software Mentioned

R

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis