Modulation of FABP4 hypomethylation by DNMT1 and its inverse interaction with miR-148a/152 in the placenta of preeclamptic rats and HTR-8 cells. (October 2016)

• Record Type: Journal Article
• Authors: Yang, Anning; Zhang, Huiping; Sun, Yue; Wang, Yanhua; Yang, Xiaoming; Yang, Xiaoling; Zhang, Hui; Guo, Wei; Zhu, Guangrong; Tian, Jue; Jia, Yuexia; Jiang, Yideng
• Is Part Of: Placenta. Volume 46(2016:Oct.)
• Page Start: 49
• Page End: 62
• Publication Date: 2016-10
• Subjects: Preeclampsia -- miR-148a/152 -- DNMT1 -- FABP4 -- DNA methylation; Placenta -- Periodicals; Reproduction -- Periodicals; Placenta -- Periodicals; Placenta -- Périodiques; Reproduction -- Périodiques; 612.63
• DOI: 10.1016/j.placenta.2016.08.086
• Languages: English
• ISSNs: 0143-4004

Abstract

Abstract: Inflammation and dysregulated lipid metabolism are involved in the pathogenesis of preeclampsia, and fatty acid binding protein 4 (FABP4) is known to regulate both inflammation and lipid metabolism. In the present study, we elucidated the role of FABP4 using in vitro and in vivo models of preclampsia. We found increased expression of FABP4 in the placenta of preeclamptic rats, which was further confirmed in HTR-8 cells, an extravillous trophoblast cell line, treated with L-NAME. Overexpression of FABP4 in HTR-8 cells resulted in upregulated expression of pro-inflammatory cytokines IL-6 and TNF-α, and increased lipid accumulation, suggesting that FABP4 plays a role in preeclampsia. Furthermore, downregulation of methylation in the promotor resulted in increased FABP4 expression, which was mediated by downregulated DNA methyltransferase 1 (DNMT1). Bioinformatics analysis showed that miR-148a/152 regulated the expression of DNMT1, and additional in vitro studies revealed that miR-148a/152 inhibited DNMT1 expression by directly binding to its 3′-UTR. Interestingly, DNMT1 enhanced the expression of miR-148a/152 by downregulation of methylation in its promotor. Taken together, our results showed that FABP4 may be involved in the pathogenesis of preeclampsia, and the expression of FABP4 is enhanced by miR-148a/152 mediated inhibition of DNMT1 expression. Highlights: FABP4 and miR-148a/152 were upregulated and DNMT1 was downregulated in placentae of pregnant rats and HTR-8 cells. DNMT1 overexpression increased FABP4 DNA methylation and decreased its expression in HTR-8 cells. DNMT1 is a direct target of miR-148a/152. miR-148a/152 caused FABP4 hypomethylation by targeting DNMT1 in preeclampsia. FABP4 is a potential therapeutic target for preeclampsia.