Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy (Oct 2022)

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

  • Jiang Y,
  • Wei L,
  • Zhang H,
  • Chen Y,
  • Gao P,
  • Zhang J,
  • Zhou X,
  • Zhu S,
  • Du Y,
  • Fang C,
  • Li J,
  • Feng L,
  • He M,
  • Wang S,
  • Yu J

Journal volume & issue
Vol. Volume 15
pp. 3361 – 3374

Abstract

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Yi Jiang,1 Lijie Wei,1 Huiting Zhang,1 Yuting Chen,1 Peng Gao,1 Jingyi Zhang,1 Xuan Zhou,1 Shenglan Zhu,1 Yuanyuan Du,1 Chenyun Fang,1 Jiaqi Li,2 Ling Feng,1 Mengzhou He,1 Shaoshuai Wang,1 Jun Yu1 1Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China; 2Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 33006, People’s Republic of ChinaCorrespondence: Jun Yu, Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Qiaokou District, Wuhan, Hubei Province, People’s Republic of China, Email [email protected]: 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, microRNAs, pregnancy, inflammation

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