Mechanism of KLF7 in regulating the proliferation and apoptosis of granulosa cells in polycystic ovarian syndrome.

Objective: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with the function of granulosa cells. This study was conducted to explore the regulatory mechanism of Kruppel-like factor 7 (KLF7) in the proliferation and apoptosis of granulosa cells and provide a rationale for the treatment of PCOS. Methods: Immortalized human ovarian granulosa cells HGL5 were cultured in vitro and treated with dihydrotestosterone (DHT) to establish the PCOS cell model. HGL5 cells were transfected with KLF7 and phosphodiesterase 4 (PDE4) overexpression vectors, and the KLF7/PDE4 expression levels in HGL5 cells were determined by qRT-PCR and Western blot. Cell viability, apoptosis, and proliferation were assessed by CCK-8, TUNEL staining, and EdU assays. The interaction between PDE4 promoter and KLF7 was testified by chromatin immunoprecipitation and dual-luciferase assay. Collaborative experiments were conducted to validate the mechanism. Results: KLF7 was downregulated in DHT-treated HGL5 cells. KLF7 overexpression facilitated the proliferation and inhibited the apoptosis of DHT-treated HGL5 cells. KLF7 bound to the PDE4 promoter and then repressed its transcription and protein levels. PDE4 overexpression neutralized the effects of KLF7 overexpression on DHT-treated HGL5 cells. Conclusion: KLF7 inhibits apoptosis and promotes proliferation of PCOS cells by transcriptionally inhibiting PDE4 expression.