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Updated: Jan 7, 2026

Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin
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IL‑1 receptor antagonism attenuates renal fibrosis via RNF182‑driven MFN2 destabilization and mitochondrial

Bo Yang1, Qing Shao1, Wei Wang1

  • 1Department of Nephrology, Naval Medical Center of PLA, Naval Medical University, Shanghai, China.

Cell Death Discovery
|December 29, 2025
PubMed

Insights

Recombinant human IL-1 receptor antagonist (rhIL-1Ra) combats kidney fibrosis by targeting the IL-1R/RNF182/MFN2 pathway. This therapy preserves mitochondrial function and reduces inflammation, offering a potential treatment for chronic kidney disease (CKD).

Area of Science:

  • Nephrology
  • Molecular Biology
  • Immunology

Background:

  • Renal fibrosis drives chronic kidney disease (CKD) progression, with limited targeted therapies.
  • Interleukin-1 (IL-1)-mediated inflammation and mitochondrial dysfunction are implicated in CKD, but their precise links are unclear.

Purpose of the Study:

  • To investigate the therapeutic potential of recombinant human IL-1 receptor antagonist (rhIL-1Ra) in kidney injury models.
  • To elucidate the molecular mechanisms linking IL-1 signaling, fibrosis, and mitochondrial homeostasis.

Main Methods:

  • Utilized acute (UUO) and chronic (5/6Nx) mouse models of kidney injury.
  • Employed in vitro studies with TGF-β1-stimulated kidney cells.
  • Investigated the role of E3 ubiquitin ligase RNF182 and mitochondrial protein MFN2.

Main Results:

  • rhIL-1Ra significantly reduced renal fibrosis, inflammation, and improved kidney function in vivo.
  • rhIL-1Ra inhibited TGF-β1-induced RNF182 expression, preventing MFN2 degradation and subsequent mitochondrial dysfunction.
  • Stabilization of MFN2 by rhIL-1Ra preserved mitochondrial respiration, ATP production, and reduced oxidative stress.

Conclusions:

  • A novel IL-1R/RNF182/MFN2 pathway links inflammation to mitochondrial and fibrotic pathology in the kidney.
  • RNF182 is identified as a key mediator of mitochondrial dysfunction in fibrosis.
  • rhIL-1Ra demonstrates therapeutic promise for CKD by targeting this pathway.

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