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Long noncoding RNA X-inactive specific transcript regulates nlr family pyrin domain containing 3/caspase-1-mediated pyroptosis in diabetic nephropathy

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World Journal of Diabetes 2022年第4期13卷 358-375页

作者： Jia Xu Qin Wang Yi-Fan Song Xiao-Hui Xu He Zhu Pei-Dan Chen Ye-Ping Ren Department of Nephrology Shenzhen University General HospitalShenzhen 518000Guangdong ProvinceChina

BACKGROUND nlrP3-mediated pyroptosis is recognized as an essential modulator of renal disease *** noncoding RNAs(lncRNAs)are active participators of diabetic nephropathy(DN).X inactive specific transcript(XIST)expression has been reported to be elevated in the serum of DN *** To evaluate the mechanism of lncRNA XIST in renal tubular epithelial cell(RTEC)pyroptosis in *** A DN rat model was established through streptozotocin injection,and XIST was knocked down by tail vein injection of the lentivirus LV *** metabolic and biochemical indices were detected,and pathological changes in the renal tissue were *** expression of indicators related to inflammation and pyroptosis was also *** glucose(HG)was used to treat HK2 cells,and cell viability and lactate dehydrogenase(LDH)activity were detected after silencing *** subcellular localization and downstream mechanism of XIST were ***,a rescue experiment was carried out to verify that XIST regulates nlr family pyrin domain containing 3(nlrP3)/caspase-1-mediated RTEC pyroptosis through the microRNA-15-5p(miR-15b-5p)/Toll-like receptor 4(TLR4)*** XIST was highly expressed in the DN *** silencing improved renal metabolism and biochemical indices and mitigated renal *** expression of inflammation and pyroptosis indicators was significantly increased in DN rats and HG-treated HK2 cells;cell viability was decreased and LDH activity was increased after HGtreatment. Silencing XIST inhibited RTEC pyroptosis by inhibiting nlrP3/caspase-1. Mechanistically,XIST sponged miR-15b-5p to regulate TLR4. Silencing XIST inhibited TLR4 by promotingmiR-15b-5p. miR-15b-5p inhibition or TLR4 overexpression averted the inhibitory effect ofsilencing XIST on HG-induced RTEC *** XIST inhibits TLR4 by upregulating miR-15b-5p and ultimately inhibits renal injury inDN by inhibiting nlrP3/caspase-1-mediated RTEC pyroptosis.

关键词： Diabetic nephropathy Pyroptosis Renal tubular epithelial cell Long noncoding RNA X-inactive specific transcript microRNA-15b-5p Toll-like receptor 4 nlr family pyrin domain containing 3/caspase-1 pathway

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