The role of TXNIP/NLRP3 pathway in migration and invasion of placental trophoblasts in gestational diabetes mellitus / 中华内分泌外科杂志

ABSTRACT

Objective:To investigate the expressions of thioredoxin-interacting protein (TXNIP) /NLR family pyrin domain containing 3 (NLRP3) pathway in placental tissues of gestational diabetes mellitus (GDM) patients and its role in the migration and invasion of placental trophoblast cells.Methods:The placenta tissues of 25 GDM pregnant women (GDM group) and 25 normal glucose tolerance pregnant women (normal group) were collected. The cultured human chorionic trophoblast cells were divided into control group (untransfected) , siNC group (negative control) , siTXNIP group (siRNA-TXNIP) , siTXNIP+pcDNA group (co transfected with siRNA-TXNIP and pcDNA3.1 empty vector plasmids) and siTXNIP + NLRP3 group (co transfected with siRNA-TXNIP and pcDNA3.1-Flag-NLRP3 over expression plasmids) . The expressions of TXNIP and NLRP3 mRNAs were detected by real-time fluorescence quantitative PCR, and the expressions of TXNIP and NLRP3 proteins were detected by Western blot. Cell viability was measured by thiazole blue method. Cell migration ability was detected by scratch test, and cell invasion was detected by Transwell’s cell experiment.Results:Compared with those in the normal group, mRNA and protein expression levels of TXNIP and NLRP3 in the placenta of patients in GDM group were significantly higher ( P<0.05) . Compared with those in the control group or siNC group, mRNA and protein expression levels of TXNIP in siTXNIP group were significantly lower, however, the cell viability and migration rate were significantly higher, and the number of transmembrane cells was significantly higher ( P<0.05) ; but there was no significant difference in the above indexes between siNC group and the control group ( P>0.05) . Compared with those in siTXNIP group or siTXNIP + pcDNA group, mRNA and protein expression levels of NLRP3 in siTXNIP + NLRP3 group were significantly higher, however, the cell viability and migration rate were significantly lower, and the number of transmembrane cells was significantly lower ( P<0.05) ; but there was no significant difference in the above indexes between siTXNIP + pcDNA group and siTXNIP group ( P>0.05) . Conclusions:TXNIP/NLRP3 pathway is closely related to the occurrence and development of GDM. TXNIP can inhibit the migration and invasion of placental trophoblast cells by activating NLRP3.