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中华消化病与影像杂志(电子版) ›› 2026, Vol. 16 ›› Issue (04) : 294 -301. doi: 10.3877/cma.j.issn.2095-2015.2026.04.002

论著

KLF4调控TXNIP介导线粒体氧化应激激活AR42J细胞NLRP3炎症小体的机制研究
任伟洁1, 毛妮2, 胡宁丹1, 沈锋2,()   
  1. 1310000 杭州,浙江省立同德医院重症监护室
    2310000 杭州,浙江省立同德医院肛肠外科
  • 收稿日期:2026-03-30 出版日期:2026-08-01
  • 通信作者: 沈锋
  • 基金资助:
    浙江省中医药科技计划项目(2021ZB049)

KLF4 activates NLRP3 inflammasomes in AR42J cells by modulating TXNIP-mediated mitochondrial oxidative stress

Weijie Ren1, Ni Mao2, Ningdan Hu1, Feng Shen2,()   

  1. 1Department of Intensive Care, Zhejiang Tongde Hospital, Hangzhou 310000, China
    2Department of Anorectal Surgery, Zhejiang Tongde Hospital, Hangzhou 310000, China
  • Received:2026-03-30 Published:2026-08-01
  • Corresponding author: Feng Shen
引用本文:

任伟洁, 毛妮, 胡宁丹, 沈锋. KLF4调控TXNIP介导线粒体氧化应激激活AR42J细胞NLRP3炎症小体的机制研究[J/OL]. 中华消化病与影像杂志(电子版), 2026, 16(04): 294-301.

Weijie Ren, Ni Mao, Ningdan Hu, Feng Shen. KLF4 activates NLRP3 inflammasomes in AR42J cells by modulating TXNIP-mediated mitochondrial oxidative stress[J/OL]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2026, 16(04): 294-301.

目的

探讨转录因子Krüppel样因子4(KLF4)在急性胰腺炎(AP)腺泡细胞损伤中的作用及分子机制,是否通过TXNIP/mtROS/NLRP3轴介导细胞焦亡。

方法

采用雨蛙素(100 nmol/L,3 h)刺激AR42J细胞建立AP模型,设对照、模型、si-NC、si-KLF4及si-KLF4+MitoPQ组。检测细胞活力、损伤标志物、焦亡相关蛋白、线粒体功能、mtROS、TXNIP-NLRP3共定位。

结果

AP中KLF4上调;敲低KLF4可改善细胞活力与损伤,抑制NLRP3炎症小体活化、细胞焦亡,下调TXNIP,改善线粒体功能,减少mtROS,并减弱TXNIP-NLRP3共定位;外源性mtROS可部分逆转上述保护效应。

结论

KLF4通过调控TXNIP/mtROS轴激活NLRP3炎症小体,介导AP腺泡细胞焦亡。

Objective

To investigate the role and molecular mechanism of the transcription factor Krüppel-like factor 4 (KLF4) in acinar cell injury in acute pancreatitis (AP), and whether it mediates pyroptosis through the TXNIP/mtROS/NLRP3 axis.

Methods

AR42J cells were stimulated with cerulein (100 nmol/L, 3 h) to establish an AP model. The cells were divided into control, model, si-NC, si-KLF4, and si-KLF4+MitoPQ groups. Cell viability, injury markers, pyroptosis-related proteins, mitochondrial function, mtROS, TXNIP-NLRP3 colocalization were detected.

Results

KLF4 was upregulated in AP. Knockdown of KLF4 improved cell viability and reduced injury, inhibited NLRP3 inflammasome activation, pyroptosis, downregulated TXNIP, improved mitochondrial function, decreased mtROS, and attenuated TXNIP-NLRP3 colocalization. Exogenous mtROS partially reversed these protective effects.

Conclusion

KLF4 activates the NLRP3 inflammasome by regulating the TXNIP/mtROS axis, thereby mediating pyroptosis of acinar cells in AP.

图1 KLF4敲低对雨蛙素诱导的AR42J细胞损伤的影响 1A:细胞活力;1B:淀粉酶释放量;1C:LDH释放量注:组间比较采用单因素方差分析,两两比较采用Tukey法;***P<0.001,**P<0.01(n=3);AP急性胰腺炎
图2 雨蛙素处理对AR42J细胞中KLF4表达的影响 2A:Klf4 mRNA的相对表达水平;2B:Western Blot检测KLF4蛋白表达的典型条带;2C:统计分析注:组间比较采用单因素方差分析,两两比较采用Tukey法(n=3);AP急性胰腺炎
图3 敲低KLF4对雨蛙素诱导的AR42J细胞焦亡相关蛋白表达的影响 3A:Western Blot检测焦亡关键蛋白典型条带;3B~3E:统计分析注:组间比较采用单因素方差分析,两两比较采用Tukey法(n=3);AP急性胰腺炎
图4 敲低KLF4对雨蛙素诱导的AR42J细胞焦亡的影响 4A:细胞焦亡的流式典型图;4B:统计分析注:组间比较采用单因素方差分析,两两比较采用Tukey法(n=3);AP急性胰腺炎
图5 敲低KLF4对雨蛙素诱导的AR42J细胞线粒体功能的影响 5A:线粒体膜电位流式典型图;5B:统计分析;5C:ATP含量注:组间比较采用单因素方差分析,两两比较采用Tukey法(n=3);AP急性胰腺炎
图6 敲低KLF4对雨蛙素诱导的AR42J细胞线粒体应激的影响 6A:mtROS的荧光典型图;6B:统计分析注:组间比较采用单因素方差分析,两两比较采用Tukey法(n=3);AP急性胰腺炎
图7 KLF4及mtROS对TXNIP与NLRP3相互作用的影响 7A:免疫荧光染色检测TXNIP(绿色)与NLRP3(红色)共定位。7B:TXNIP荧光信号的平均荧光强度定量分析;7C:NLRP3荧光信号的平均荧光强度定量分析;7D:TXNIP与NLRP3共定位程度统计分析注:组间比较采用单因素方差分析,两两比较采用Tukey法(n=3);AP急性胰腺炎
图8 恢复mtROS对KLF4敲低细胞保护效应的逆转作用 8A:细胞活力;8B:淀粉酶释放量;8C:乳酸脱氢酶释放量注:组间比较采用单因素方差分析,两两比较采用Tukey法(n=3);AP急性胰腺炎
[1]
Iannuzzi JP, King JA, Leong JH, et al. Global incidence of acute pancreatitis is increasing over time: A systematic review and meta-analysis[J]. Gastroenterology, 2021, 162(1): 122-134.
[2]
Al Mamun A, Suchi SA, Aziz MA, et al. Pyroptosis in acute pancreatitis and its therapeutic regulation[J]. Apoptosis, 2022, 27(7/8): 465-481.
[3]
Rusetskaya NY, Loginova NY, Pokrovskaya EP, et al. Redox regulation of the NLRP3-mediated inflammation and pyroptosis[J]. Biomed Khim, 2023, 69(6): 333-352.
[4]
Yao J, Kong Q, Wang Y, et al. Mechanism of Kruppel-like factor 4 in pyroptosis of nasal mucosal epithelial cells in mice with allergic rhinitis[J]. Am J Rhinol Allergy, 2023, 37(3): 337-347.
[5]
Wang X, Yu L, Chen Y, et al. The KLF4-STAT5 axis promotes pancreatic fibrosis in mice with caerulein-induced chronic pancreatitis [J]. Exp Anim, 2023, 72(3): 379-388.
[6]
He Z, He J, Xie K. KLF4 transcription factor in tumorigenesis[J]. Cell Death Discov, 2023, 9(1): 118.
[7]
Lv H, Liu X, Zhou H. USP25 upregulation boosts GSDMD-mediated pyroptosis of acinar cells in acute pancreatitis[J]. Shock, 2022, 58(5): 408-416.
[8]
Wang X, Guo Y, Cui T, et al. Telomerase reverse transcriptase restores pancreatic microcirculation profiles and attenuates endothelial dysfunction by inhibiting mitochondrial superoxide production: A potential target for acute pancreatitis therapy[J]. Biomed Pharmacother, 2023, 167: 115576.
[9]
Chen Y, Sun L, Liu H, et al. KLF4 interacts with TXNIP to modulate the pyroptosis in ulcerative colitis via regulating NLRP3 signaling[J]. Immun Inflamm Dis, 2024, 12(2): e1199.
[10]
Li A, Zhang Y, Wang J, et al. Txnip gene knockout ameliorated HFD-induced cardiomyopathy via regulating mitochondria dynamics and fatty acid oxidation[J]. J Cardiovasc Pharmacol, 2023, 81(6): 423-433.
[11]
Peng A, Peng J, Lai R, et al. Resveratrol reduces cisplatin-induced cochlear hair cell pyroptosis by inhibiting the mtROS/TXNIP/NLRP3 pathway[J]. Comb Chem High Throughput Screen, 2025, 28(15): 2737-2749.
[12]
Lin Y, Ma X, Zhang L, et al. Investigating the Role of Salidroside in Alleviating Acute Pancreatitis by Inhibiting the RIPK1/RIPK3/MLKL Pathway-Mediated Necroptosis in Pancreatic Acinar Cells in Rats[J]. Journal of Inflammation Research, 2025, 18: 14857-14869.
[13]
高明, 王琪, 孙远松, 等. circZMYM2/miR-29a/PUMA轴对急性胰腺炎腺泡细胞凋亡的影响及作用机制[J]. 中国普通外科杂志, 2023, 32(9): 1341-1348.
[14]
Xiang H, Guo F, Tao X, et al. Pancreatic ductal deletion of S100A9 alleviates acute pancreatitis by targeting VNN1-mediated ROS release to inhibit NLRP3 activation[J]. Theranostics, 2021, 11(9): 4467-4482.
[15]
Peng Y, Yang Y, Li Y, et al. Mitochondrial(mt)DNA-cyclic GMP- AMP synthase(cGAS)-stimulator of interferon genes(STING) signaling promotes pyroptosis of macrophages via interferon regulatory factor (IRF)7/IRF3 activation to aggravate lung injury during severe acute pancreatitis[J]. Cell Mol Biol Lett, 2024, 29(1): 61.
[16]
Liang Y, Zhao J, Dai T, et al. A review of KLF4 and inflammatory disease: Current status and future perspective[J]. Pharmacol Res, 2024, 207: 107345.
[17]
Zhao Y, Feng Y, Sun F, et al. Optimized rAAV8 targeting acinar KLF4 ameliorates fibrosis in chronic pancreatitis via exosomes- enriched let-7s suppressing pancreatic stellate cells activation[J]. Mol Ther, 2024, 32(8): 2624-2640.
[18]
Chen Y, Sun L, Liu H, et al. KLF4 interacts with TXNIP to modulate the pyroptosis in ulcerative colitis via regulating NLRP3 signaling[J]. Immun Inflamm Dis, 2024, 12(2): e1199.
[19]
Ma N, Xia L, Zheng Z, et al. Silencing of TXNIP attenuates oxidative stress injury in HEI-OC1 by inhibiting the activation of NLRP3 and NF-κB[J]. Heliyon, 2024, 10(18): e37753.
[20]
Choi EH, Park SJ. TXNIP: A key protein in the cellular stress response pathway and a potential therapeutic target[J]. Exp Mol Med, 2023, 55(7): 1348-1356.
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