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This research aims to assess the effects of sgp130Fc on sepsis-associated kidney injury and its mechanisms.

March 28, 2026

Regulation of Inflammatory Responses and Apoptosis: sgp130fc as a Potential Therapeutic Agent for Sepsis-Associated Kidney Injury

XLXuefang LiuHebei Medical University YLYa LiuHebei Medical University YCYe ChenHebei Medical University

Key Points

This research aims to assess the effects of sgp130Fc on sepsis-associated kidney injury and its mechanisms.
Stratified a cohort of 60 patients into three groups based on kidney injury severity.
Induced sepsis in male mice using cecal ligation and puncture.
Administered sgp130Fc and assessed its effects on inflammatory pathways and apoptosis-related proteins.
sgp130Fc reduced the severity of sepsis-associated kidney injury.
Inhibition of IL-6 signaling decreased inflammation and apoptosis.
Downregulation of apoptosis markers Bax and upregulation of Bcl-2 were observed.

Abstract

Objective: This study aims to evaluate the therapeutic potential and underlying mechanisms of sgp130Fc, a selective inhibitor interleukin-6 (IL-6) trans-signaling, in mitigating sepsis-associated kidney injury (SAKI). Methods: A cohort of 60 patients was stratified into three groups: Sepsis group (n = 20), SAKI Stages I-II group (n = 20), and SAKI Stage III group (n = 20). A positive correlation was observed between acute kidney injury severity and IL-6 levels. In vivo , sepsis was induced in male C57BL/6J mice via cecal ligation and puncture. The therapeutic effects of sgp130Fc, a selective inhibitor of IL-6 trans-signaling, were investigated. Transcriptomic analysis (RNA-seq) of renal tissue from septic mice identified differentially expressed genes. Gene Ontology enrichment analysis confirmed significant enrichment of inflammation-related pathways, further validated using hypergeometric testing with an inflammation-specific gene set. Expression of downstream signaling molecules (signal transducer and activator of transcription 3 STAT3, nuclear factor kappa-light-chain-enhancer of activated B cells NF-κB, apoptosis-related proteins (B-cell lymphoma 2 Bcl-2, Bcl-2-associated X protein Bax), and renal injury biomarkers (kidney injury molecule-1 KIM-1, neutrophil gelatinase-associated lipocalin NGAL) was also assessed. Results: Administration of sgp130Fc attenuated SAKI through inhibition of IL-6/sIL-6R signaling and modulation of the STAT3/NF-κB pathway. This intervention resulted in reduced release of pro-inflammatory mediators and decreased apoptosis as evidenced by downregulation of Bax, upregulation of Bcl-2, and reductions in renal injury markers KIM-1 and NGAL. Conclusion: sgp130Fc confers renoprotective effects in a murine model of sepsis by selectively targeting the IL-6 trans-signaling pathway and modulating STAT3/NF-κB signaling to inhibit inflammation and apoptosis. These findings highlight the therapeutic potential of sgp130Fc in SAKI and support further clinical investigation.

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