RNF130 ameliorates renal injury and inflammation by inhibiting macrophage pyroptosis through ubiquitination degradation of PDCD4 in male mice.

RNF130 is significantly downregulated in mice and patients with acute kidney injury, and myeloid-specific loss worsens renal damage by promoting macrophage pyroptosis in AKI models.

• Why it matters: Macrophage pyroptosis contributes to AKI, but the molecular pathway linking RNF130 to inflammasome-driven cell death was unclear.
• What they did: The study used AKI mouse models with myeloid-specific RNF130 loss, proteomics plus validation to show RNF130 prevents PDCD4 ubiquitination at lysine 402, thereby limiting NF-κB/STAT3 signaling and NLRP3 inflammasome activation.
• The result: PDCD4 overexpression nullified RNF130’s protective effect, and Nystose mitigated ischemic AKI renal injury in mice by targeting and upregulating RNF130.

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