ABSTRACT
BACKGROUND: Krüppel-like factor 15 (KLF15) has been reported to be involved in ischemia injury of multiple types of diseases. Nevertheless, the roles and underlying mechanisms of KLF15 in preeclampsia (PE) are still unclear. METHODS: In this study, the expression of KLF15 in placenta tissues and hypoxia/reoxygenation (H/R)-induced HTR8/SVneo cells was evaluated by GSE66273 database, qRT-PCR and western blot assay. CCK-8 assay was employed to detect cell proliferation. Wound healing assay and transwell assay were used to detect cell migration and invasion. Cell oxidative stress was measured by DCFH-DA staining and kits. Cell apoptosis was evaluated by TUNEL assay and western blot assay. The JASPAR database was used to analyze the binding site of KLF15 and insulin-like growth factor-1 receptor (IGF1R) promoter region. The luciferase reporter assay was used to detect IGF1R promoter activity and ChIP assay was used to verify the combination of KLF15 and IGF1R promoter. Moreover, western blot was employed to measure the expressions of PI3K/Akt-related proteins. RESULTS: The data showed that the expression of KLF15 was significantly downregulated in GSE66273 database, tissues and HTR8/SVneo cells. KLF15 overexpression increased H/R-induced HTR8/SVneo cell proliferation, invasion and migration, and inhibited oxidative stress and cell apoptosis. In addition, IGF1R was highly expressed in H/R-induced HTR8/SVneo cells after KLF15 overexpression, and the binding of KLF15 and IGF1R promoter was verified. Silencing of IGF1R reversed the effects of KLF15 overexpression on H/R-induced HTR8/SVneo cell proliferation, migration, invasion, oxidative stress and cell apoptosis. Moreover, KLF15 overexpression and IGF1R silencing regulated the expressions of PI3K/Akt-related proteins in H/R-induced HTR8/SVneo cells. CONCLUSION: In conclusion, KLF15 overexpression promoted the proliferation and metastasis, and suppressed oxidative stress and cell apoptosis of H/R-induced HTR8/SVneo cells through mediating the PI3K/Akt pathway, which may provide a promising target for the treatment of preeclampsia.
