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Updated: Jul 17, 2026

Cecal Ligation and Puncture-induced Sepsis as a Model To Study Autophagy in Mice
06:40

Cecal Ligation and Puncture-induced Sepsis as a Model To Study Autophagy in Mice

Published on: February 9, 2014

METTL3/FOSL1-associated inflammatory and autophagy-related responses involve m6A-related regulation in sepsis-induced

Feifei Shao1, Junhao Pan1, Qingqing Yan1

  • 1Department of Intensive Care Unit, Taizhou First People's Hospital, Taizhou, Zhejiang Province, 318020, China.

Archives of Biochemistry and Biophysics
|July 15, 2026
PubMed
Abstract

Insights

Sepsis-induced acute kidney injury (S-AKI) involves inflammation and autophagy changes. METTL3 regulates FOSL1 via m6A modification, impacting S-AKI progression and offering potential therapeutic targets.

Area of Science:

  • Molecular Biology
  • Renal Physiology
  • Immunology

Background:

  • Sepsis-induced acute kidney injury (S-AKI) is characterized by tubular damage, inflammation, and altered autophagy.
  • N6-methyladenosine (m6A) RNA modification is a key regulator of cellular stress responses, but its role in S-AKI is not fully understood.

Purpose of the Study:

  • To investigate the role and regulatory mechanisms of m6A modification, specifically METTL3 and FOSL1, in the pathogenesis of S-AKI.
  • To elucidate the relationship between METTL3, FOSL1, and downstream signaling pathways in S-AKI.

Main Methods:

  • Established in vitro (LPS-stimulated HK-2 cells) and in vivo (CLP-induced mice) S-AKI models.
  • Assessed global m6A levels, METTL3, and FOSL1 expression using ELISA, qRT-PCR, and Western blot.
  • Utilized siRNA, overexpression, and inhibitors to determine functional roles; employed MeRIP-qPCR and RIP-qPCR to investigate m6A enrichment and METTL3-FOSL1 association.

Main Results:

  • LPS stimulation upregulated m6A, METTL3, and FOSL1 in HK-2 cells, increasing inflammation and autophagy changes.
  • METTL3 influenced FOSL1 mRNA stability via m6A modification; FOSL1 knockdown attenuated S-AKI markers.
  • In vivo, METTL3 knockdown ameliorated S-AKI, improving renal function and reducing injury by modulating FOSL1 expression and related signaling pathways (NF-κB, mTOR).

Conclusions:

  • METTL3/FOSL1 axis, through m6A-dependent regulation, contributes to inflammation and autophagy alterations in S-AKI.
  • These findings highlight the significance of m6A-related regulatory mechanisms in S-AKI pathogenesis and suggest potential therapeutic targets.
Keywords:
AutophagyFOSL1METTL3Sepsis-induced acute kidney injurym6A RNA methylation

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