BCAM Deficiency May Contribute to Preeclampsia by Suppressing the PIK3R6/p-STAT3 Signaling. Issue 12 (12th October 2022)

• Record Type: Journal Article
• Authors: Liu, Min; Liao, Lingyun; Gao, Yijie; Yin, Yangxue; Wei, Xiaohong; Xu, Qin; Gao, Linbo; Zhou, Rong
• Is Part Of: Hypertension. Volume 79:Issue 12(2022)
• Page Start: 2830
• Page End: 2842
• Publication Date: 2022-10-12
• Subjects: preeclampsia -- basal cell adhesion molecule -- miRNAs -- rats -- trophoblast cells; Hypertension -- Periodicals; Hypertension -- Treatment -- Periodicals; 616.132005
• DOI: 10.1161/HYPERTENSIONAHA.122.20085
• Languages: English
• ISSNs: 0194-911X

Abstract

Abstract : Background: Preeclampsia is a pregnancy syndrome that may utilize multiple pathogenic mechanisms. Insufficient trophoblast invasion and impaired uterine spiral artery remodeling are believed to be the pathological basis; yet the underlying mechanisms remain largely unclear. Methods: The placental BCAM (basal cell adhesion molecule) expression and important clinical indicators were detected and correlation analysis was performed. MiRNAs directly targeting BCAM were predicted and further verified by dual-luciferase reporter gene, and the downstream molecular mechanisms of BCAM were investigated in both HTR-8/SVneo and JAR cells. In addition, pregnant/nonpregnant rats were treated with adenoviruses containing BCAM shRNA genes (Ad-shBCAM) on gestational 9.5 days to detect the preeclamptic features. Results: The BCAM is highly expressed on the trophoblast membrane and decreased in the preeclamptic placentae. In HTR-8/SVneo and JAR cells, BCAM knockdown inhibited trophoblast proliferation, migration, and invasion, and suppressed phosphorylation on Y705 of STAT3 dependent on the downregulation of PIK3R6. Moreover, miR-199a-5p mediated the degradation of BCAM and also inhibited trophoblast proliferation, migration, and invasion. In vivo, BCAM deficiency induced a preeclampsia-like phenotype included elevated systolic blood pressure, proteinuria, impaired morphology and function of multiple organs (placenta, liver, and kidney), and fetal growth restriction. The expression of placenta BCAM/PIK3R6/p-STAT3 signaling was also downregulated in this preeclampsia rat model. Conclusions: MiR-199a-5p mediated–BCAM deficiency contributes to the suppression of trophoblast proliferation, migration, and invasion by inhibiting PIK3R6/p-STAT3 signaling, which may lead to poor placentation and result in preeclampsia-like phenotypes. Our study provides a new academic perspective on the pathogenesis of preeclampsia.