BACKGROUND NLRP3-mediated pyroptosis is recognized as an essential modulator of renal disease pathology.Long noncoding RNAs(lncRNAs)are active participators of diabetic nephropathy(DN).X inactive specific transcript(X...BACKGROUND NLRP3-mediated pyroptosis is recognized as an essential modulator of renal disease pathology.Long 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 patients.AIM To evaluate the mechanism of lncRNA XIST in renal tubular epithelial cell(RTEC)pyroptosis in DN.METHODS A DN rat model was established through streptozotocin injection,and XIST was knocked down by tail vein injection of the lentivirus LV sh-XIST.Renal metabolic and biochemical indices were detected,and pathological changes in the renal tissue were assessed.The expression of indicators related to inflammation and pyroptosis was also detected.High glucose(HG)was used to treat HK2 cells,and cell viability and lactate dehydrogenase(LDH)activity were detected after silencing XIST.The subcellular localization and downstream mechanism of XIST were investigated.Finally,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)axis.RESULTS XIST was highly expressed in the DN models.XIST silencing improved renal metabolism and biochemical indices and mitigated renal injury.The 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 pyroptosis.CONCLUSIONSilencing XIST inhibits TLR4 by upregulating miR-15b-5p and ultimately inhibits renal injury inDN by inhibiting NLRP3/caspase-1-mediated RTEC pyroptosis.展开更多
目的研究术前NLR家族Pyrin域蛋白3(NLR family pyrin domain-containing protein 3,NLRP3)、白细胞介素(Interleukin,ILs)表达谱特征对神经胶质瘤患者手术预后的影响。方法以2019年1月-2022年12月新疆医科大学第二附属医院神经外科收治...目的研究术前NLR家族Pyrin域蛋白3(NLR family pyrin domain-containing protein 3,NLRP3)、白细胞介素(Interleukin,ILs)表达谱特征对神经胶质瘤患者手术预后的影响。方法以2019年1月-2022年12月新疆医科大学第二附属医院神经外科收治的86例神经胶质瘤患者为研究对象,根据患者术后1年内随访情况将患者划分为手术预后良好组(n=52)和手术预后不良组(n=34)。对比两组患者一般临床资料及术前NLRP3、ILs(IL-1β、IL-4、IL-12、IL-17、IL-33)表达谱的表达水平差异。采用Spearman相关性分析,经单因素及多因素Logistic回归分析筛选神经胶质瘤患者手术预后不良的危险因素,通过受试者工作特征(Receiver operating characteristic,ROC)曲线评价各危险因素对患者手术预后的影响。结果与手术预后良好组比较,手术预后不良组患者肿瘤大小、肿瘤周围水肿患者比例、合并癫痫发作史患者比例、血清NLRP3、IL-1β、IL-4、IL-33水平均升高,术前卡氏功能状态评分、血清IL-12水平均降低,差异有统计学意义(P<0.05);Spearman相关性分析结果表明,肿瘤大小、肿瘤周围水肿、有癫痫发作史、血清中NLRP3、IL-1β、IL-4、IL-33水平均与手术预后不良呈正相关性,卡氏功能状态评分、IL-12与手术预后不良呈负相关性(P<0.05);单因素及多因素Logistic回归分析表明血清中NLRP3、IL-1β、IL-4水平均是神经胶质瘤患者手术预后不良的重要危险因素,IL-12是神经胶质瘤患者手术预后不良的重要保护因素(P<0.05);ROC曲线分析表明NLRP3、IL-1β、IL-4、IL-12独立及联合对于神经胶质瘤患者手术预后不良均具有较高预测效能(P<0.05)。结论神经胶质瘤患者NLRP3、ILs水平较高均是手术预后不良的重要危险因素,通过早期干预减轻神经胶质瘤患者炎症水平可能有利于改善手术治疗效果。展开更多
基金Supported by Natural Science Foundation of Shenzhen University General Hospital (SUGH2020QD011)
文摘BACKGROUND NLRP3-mediated pyroptosis is recognized as an essential modulator of renal disease pathology.Long 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 patients.AIM To evaluate the mechanism of lncRNA XIST in renal tubular epithelial cell(RTEC)pyroptosis in DN.METHODS A DN rat model was established through streptozotocin injection,and XIST was knocked down by tail vein injection of the lentivirus LV sh-XIST.Renal metabolic and biochemical indices were detected,and pathological changes in the renal tissue were assessed.The expression of indicators related to inflammation and pyroptosis was also detected.High glucose(HG)was used to treat HK2 cells,and cell viability and lactate dehydrogenase(LDH)activity were detected after silencing XIST.The subcellular localization and downstream mechanism of XIST were investigated.Finally,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)axis.RESULTS XIST was highly expressed in the DN models.XIST silencing improved renal metabolism and biochemical indices and mitigated renal injury.The 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 pyroptosis.CONCLUSIONSilencing XIST inhibits TLR4 by upregulating miR-15b-5p and ultimately inhibits renal injury inDN by inhibiting NLRP3/caspase-1-mediated RTEC pyroptosis.
文摘目的研究术前NLR家族Pyrin域蛋白3(NLR family pyrin domain-containing protein 3,NLRP3)、白细胞介素(Interleukin,ILs)表达谱特征对神经胶质瘤患者手术预后的影响。方法以2019年1月-2022年12月新疆医科大学第二附属医院神经外科收治的86例神经胶质瘤患者为研究对象,根据患者术后1年内随访情况将患者划分为手术预后良好组(n=52)和手术预后不良组(n=34)。对比两组患者一般临床资料及术前NLRP3、ILs(IL-1β、IL-4、IL-12、IL-17、IL-33)表达谱的表达水平差异。采用Spearman相关性分析,经单因素及多因素Logistic回归分析筛选神经胶质瘤患者手术预后不良的危险因素,通过受试者工作特征(Receiver operating characteristic,ROC)曲线评价各危险因素对患者手术预后的影响。结果与手术预后良好组比较,手术预后不良组患者肿瘤大小、肿瘤周围水肿患者比例、合并癫痫发作史患者比例、血清NLRP3、IL-1β、IL-4、IL-33水平均升高,术前卡氏功能状态评分、血清IL-12水平均降低,差异有统计学意义(P<0.05);Spearman相关性分析结果表明,肿瘤大小、肿瘤周围水肿、有癫痫发作史、血清中NLRP3、IL-1β、IL-4、IL-33水平均与手术预后不良呈正相关性,卡氏功能状态评分、IL-12与手术预后不良呈负相关性(P<0.05);单因素及多因素Logistic回归分析表明血清中NLRP3、IL-1β、IL-4水平均是神经胶质瘤患者手术预后不良的重要危险因素,IL-12是神经胶质瘤患者手术预后不良的重要保护因素(P<0.05);ROC曲线分析表明NLRP3、IL-1β、IL-4、IL-12独立及联合对于神经胶质瘤患者手术预后不良均具有较高预测效能(P<0.05)。结论神经胶质瘤患者NLRP3、ILs水平较高均是手术预后不良的重要危险因素,通过早期干预减轻神经胶质瘤患者炎症水平可能有利于改善手术治疗效果。
