miR-17-5p Promotes Glucose Uptake of HTR8/SVneo Trophoblast Cells by Inhibiting TXNIP/NLRP3 Inflammasome Pathway

Yi Jiang; Lijie Wei; Huiting Zhang; Yuting Chen; Peng Gao; Jingyi Zhang; Xuan Zhou; Shenglan Zhu; Yuanyuan Du; Chenyun Fang; Jiaqi Li; Ling Feng; Mengzhou He; Shaoshuai Wang; Jun Yu

doi:10.2147/DMSO.S385774

miR-17-5p Promotes Glucose Uptake of HTR8/SVneo Trophoblast Cells by Inhibiting TXNIP/NLRP3 Inflammasome Pathway

Diabetes Metab Syndr Obes. 2022 Oct 31:15:3361-3374. doi: 10.2147/DMSO.S385774. eCollection 2022.

Authors

Yi Jiang¹, Lijie Wei¹, Huiting Zhang¹, Yuting Chen¹, Peng Gao¹, Jingyi Zhang¹, Xuan Zhou¹, Shenglan Zhu¹, Yuanyuan Du¹, Chenyun Fang¹, Jiaqi Li², Ling Feng¹, Mengzhou He¹, Shaoshuai Wang¹, Jun Yu¹

Affiliations

¹ Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People's Republic of China.
² Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 33006, People's Republic of China.

Abstract

Introduction: Gestational diabetes mellitus (GDM) is one of the common metabolic disorders of pregnancy and results in poor pregnancy outcomes for both mother and fetus. MiR-17-5p is considered as the strongest predictor of metabolic syndrome status, but the relationship between GDM and miR-17-5p remains unclear. TXNIP, which leads to activation of NLRP3, is considered as a potential target of miR-17-5p, and the miR-17-5p/TXNIP/NLRP3 axis has been shown to play a major role in the occurrence and development of many metabolic diseases but has not been validated in GDM.

Methods: MiR-17-5p was detected by RT-qPCR. The expression of TXNIP and NLRP3 in placenta was detected by immunofluorescence, RT-qPCR and Western blot. To explore the effect of miR-17-5p on TXNIP and NLRP3 and glucose uptake of HTR8/SVneo cells, miR-17-5p mimic and miR-17-5p inhibitor were transfected to achieve overexpression and inhibition. The interaction between miR-17-5p and TXNIP was confirmed by dual-luciferase reporter assay. Besides, glucose consumption of trophoblast cells was detected by glucose assay kit.

Results: MiR-17-5p expression was down-regulated, while the expression of TXNIP and NLRP3 was up-regulated in GDM placental tissues. MiR-17-5p targeted TXNIP and inhibited its expression. MiR-17-5p also regulated NLRP3 expression and glucose uptake of HTR8/SVneo cells, which could be reversed by overexpression of TXNIP, suggesting that miR-17-5p improved glucose uptake of HTR8/SVneo cells by TXNIP/NLRP3 axis. The results were consistent with the above findings in high-glucose treated HTR8/SVneo cells.

Conclusion: Our results suggested that miR-17-5p ameliorates the glucose uptake of HTR8/SVneo cells by TXNIP/NLRP3 axis, which may provide a new idea for offspring health of GDM patients.

Keywords: diabetes; gestational; inflammation; microRNAs; pregnancy.