Journal: Cell Death Discovery

Article Title: IL‑1 receptor antagonism attenuates renal fibrosis via RNF182‑driven MFN2 destabilization and mitochondrial dysfunction

doi: 10.1038/s41420-025-02929-4

Figure Lengend Snippet: In the context of kidney injury, pro-inflammatory stimuli upregulate the expression of the Interleukin-1 Receptor (IL-1R) and its downstream effector, TGF-β1, in renal tubular epithelial cells. This leads to increased expression of the E3 ubiquitin ligase RNF182. RNF182, in turn, forms a complex with the mitochondrial fusion protein Mitofusin 2 (MFN2), targeting it for ubiquitination and subsequent proteasomal degradation. The depletion of MFN2 results in mitochondrial dysfunction, characterized by excessive reactive oxygen species (ROS) production and reduced ATP synthesis, which drives the progression of renal fibrosis. Therapeutic administration of recombinant human IL-1 receptor antagonist (rhIL-1Ra) blocks IL-1R signaling. This intervention suppresses the downstream upregulation of RNF182, thereby reducing MFN2 ubiquitination and degradation. The stabilization of MFN2 protein preserves mitochondrial function, mitigates oxidative stress, and restores cellular energy production, ultimately exerting a potent anti-fibrotic effect and protecting kidney tissue.

Article Snippet: Human kidney proximal tubular epithelial cells (HK-2, ATCC CRL-2190) were cultured in DMEM/F-12 medium (Gibco, Cat# 11330032) supplemented with 10% fetal bovine serum (FBS) (Gibco, Cat# 10270106) and 1% penicillin-streptomycin (Gibco, Cat# 15140122).

Techniques: Expressing, Ubiquitin Proteomics, Recombinant