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.