The nod-like receptor protein-3 (NLRP3)-mediated pyroptosis is involved in kidney diseases. Thioredoxin interacting protein (TXNIP) directly interacts with NLRP3. This study aimed to probe the mechanism of TXNIP and NLRP3 pathway in diabetic nephropathy (DN). Marker detection and histological staining indicated that in DN rats, the renal function was destroyed, and the TXNIP/NLRP3 axis was activated to induce inflammatory generation and pyroptosis. The protein levels of TXNIP, NLRP3 inflammatory components and endoplasmic reticulum stress (ERS)-related factors (ATF4, CHOP and IRE1α) were measured. DN rats were injected with LV-TXNIP-shRNA or IRE1α RNase specific inhibitor (STF-083010) to examine ERS- and pyroptosis-related proteins, and renal injury. Silencing TXNIP inhibited the NLRP3 axis and reduced renal damage in DN rats. ERS was activated in DN rats, and miR-200a expression was degraded by IRE1α. miR-200a bound to TXNIP. NRK-52E cells were induced by high glucose (HG) to simulate DN in vitro. The damage and pyroptosis of NRK-52E cells were analyzed. After inhibiting IRE1α, miR-200a expression increased and TXNIP expression decreased. miR-200a inhibition in HG-induced NRK-52E cells partially reversed the reduced pyroptosis by STF-083010. Overall, IRE1α upregulates miR-200a degradation in DN rats, and stimulates the TXINP/NLRP3 pathway-mediated pyroptosis and renal damage.

点样受体蛋白3（NLRP3）介导的细胞凋亡与肾脏疾病有关。硫氧还蛋白相互作用蛋白（TXNIP）与NLRP3直接相互作用。本研究旨在探讨糖尿病性肾病（DN）中TXNIP和NLRP3途径的机制。标记物检测和组织学染色表明，在DN大鼠中，肾功能被破坏，并且TXNIP / NLRP3轴被激活，从而引起炎症的产生和凋亡。测量了TXNIP，NLRP3炎症成分和内质网应激（ERS）相关因子（ATF4，CHOP和IRE1α）的蛋白水平。向DN大鼠注射LV-TXNIP-shRNA或IRE1αRNase特异性抑制剂（STF-083010），以检查与ERS和凋亡相关的蛋白以及肾损伤。沉默TXNIP可抑制DN大鼠的NLRP3轴并降低肾脏损害。ERS在DN大鼠中被激活，而IRE1α降解miR-200a表达。miR-200a绑定到TXNIP。高糖（HG）诱导NRK-52E细胞模拟DN体外。分析了NRK-52E细胞的损伤和热解。抑制IRE1α后，miR-200a表达增加，而TXNIP表达减少。在HG诱导的NRK-52E细胞中对miR-200a的抑制可部分逆转STF-083010降低的凋亡。总体而言，IRE1α上调DN大鼠的miR-200a降解，并刺激TXINP / NLRP3途径介导的细胞凋亡和肾损伤。