CPT1A modulates PI3K/Akt/mTOR pathway to promote preeclampsia

• DOI: 10.1016/j.placenta.2023.01.007
• Publication Date: 2023-01-19T20:24:54Z
• Authors: Miaomiao Chen; Bingdi Chao; Jiacheng Xu; Zheng Liu; Yuelan Tao; Jie He; Jie Wang; Huan Yang; Xin Luo; Hongbo Qi
• Keywords: 0303 health sciences; Carnitine O-Palmitoyltransferase; TOR Serine-Threonine Kinases; Trophoblasts; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; Pre-Eclampsia; Pregnancy; Cell Movement; Humans; Female; Proto-Oncogene Proteins c-akt; Cell Proliferation

Preeclampsia (PE) refers to a syndrome of new-onset hypertension with multisystem involvement and damage after 20 weeks of gestation. Defective placentation due to dysregulated behaviors of trophoblast cells is considered a predominant cause of PE.Immunofluorescence (if) and Western blot were used to detect the expression and localization of Carnitine palmitoyltransferase 1A (CPT1A) in placenta. CPT1A protein was overexpressed/knocked down in HTR8/SVneo cells by lentiviral/siRNA interference method. CCK-8 Assay, Western blot, flow cytometry, Wound healing and Transwell assay were used to detect the functional impact of CPT1A on HTR8/SVneo cells. Transcriptomics and bioinformatics analysis were used to predict the possible pathway of CPT1A participating in PE.CPT1A was upregulated in preeclamptic placentas when compared with normal controls. The abnormal expression of CPT1A in HTR8/SVneo cells is associated with the invasion and migration of HTR8/SVneo cells but is not related to the proliferation, cycle, and apoptosis of HTR8/SVneo cells. The results of Transcriptomic and Western blots suggest that phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway are activated in the si-CPT1A-1796 group. Compared with the si-NC group, the epithelial-mesenchymal transition (EMT) process of HTR8/SVneo cells in the si-CPT1A- 1796 group was significantly enhanced.CPT1A may participate in the pathogenesis of PE by inhibiting the EMT process of HTR8/SVneo cells through the PI3K/AKT/mTOR signaling axis. Thus, the newly unveiled novel function of CPT1A in PE via the PI3K/Akt/mTOR pathway provides a novel insight into the pathogenesis of PE.