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

doi:10.3877/cma.j.issn.2095-2015.2026.04.002

Abstract

Abstract:

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.

Key words: Acute pancreatitis, Krüppel-like factor 4, Thioredoxin-interacting protein, Mitochondrial reactive oxygen species, NOD-like receptor thermal protein domain-associated protein 3, Pyroptosis

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

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URL: https://zhxhbyyxzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2095-2015.2026.04.002

https://zhxhbyyxzz.cma-cmc.com.cn/EN/Y2026/V16/I04/294

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References 20

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