Open Access

miRNA‑21 promotes the progression of acute liver failure via the KLF6/autophagy/IL‑23 signaling pathway

  • Authors:
    • Suxia Bao
    • Weiyang Zheng
    • Rong Yan
    • Jie Xu
  • View Affiliations

  • Published online on: March 19, 2024     https://doi.org/10.3892/mmr.2024.13205
  • Article Number: 80
  • Copyright: © Bao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Acute liver failure (ALF) is a complex syndrome characterized by overactivation of innate immunity, and the recruitment and differentiation of immune cells at inflammatory sites. The present study aimed to explore the role of microRNA (miRNA/miR)‑21 and its potential mechanisms underlying inflammatory responses in ALF. Baseline serum miR‑21 was analyzed in patients with ALF and healthy controls. In addition, miR‑21 antagomir was injected via the tail vein into C57BL/6 mice, and lipopolysaccharide/D‑galactosamine (LPS/GalN) was injected into mice after 48 h. The expression levels of miR‑21, Krüppel‑like‑factor‑6 (KLF6), autophagy‑related proteins and interleukin (IL)‑23, and hepatic pathology were then assessed in the liver tissue. Furthermore, THP‑1‑derived macrophages were transfected with a miRNA negative control, miR‑21 inhibitor, miR‑21 mimics or KLF6 overexpression plasmid, followed by treatment with or without rapamycin, and the expression levels of miR‑21, KLF6, autophagy‑related proteins and IL‑23 were evaluated. The results revealed that baseline serum miR‑21 levels were significantly upregulated in patients with ALF. In addition, LPS/GalN‑induced ALF was attenuated in the antagomir‑21 mouse group. KLF6 was identified as a target of miR‑21‑5p with one putative seed match site identified by TargetScan. A subsequent luciferase activity assay demonstrated a direct interaction between miR‑21‑5p and the 3'‑UTR of KLF6 mRNA. Further experiments suggested that miR‑21 promoted the expression of IL‑23 via inhibiting KLF6, which regulated autophagy. In conclusion, in the present study, baseline serum miR‑21 levels were highly upregulated in patients with ALF, antagomir‑21 attenuated LPS/GalN‑induced ALF in a mouse model, and miR‑21 could promote the expression of IL‑23 via inhibiting KLF6.
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May-2024
Volume 29 Issue 5

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Copy and paste a formatted citation
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Spandidos Publications style
Bao S, Zheng W, Yan R and Xu J: miRNA‑21 promotes the progression of acute liver failure via the KLF6/autophagy/IL‑23 signaling pathway. Mol Med Rep 29: 80, 2024.
APA
Bao, S., Zheng, W., Yan, R., & Xu, J. (2024). miRNA‑21 promotes the progression of acute liver failure via the KLF6/autophagy/IL‑23 signaling pathway. Molecular Medicine Reports, 29, 80. https://doi.org/10.3892/mmr.2024.13205
MLA
Bao, S., Zheng, W., Yan, R., Xu, J."miRNA‑21 promotes the progression of acute liver failure via the KLF6/autophagy/IL‑23 signaling pathway". Molecular Medicine Reports 29.5 (2024): 80.
Chicago
Bao, S., Zheng, W., Yan, R., Xu, J."miRNA‑21 promotes the progression of acute liver failure via the KLF6/autophagy/IL‑23 signaling pathway". Molecular Medicine Reports 29, no. 5 (2024): 80. https://doi.org/10.3892/mmr.2024.13205