HNRNPC-Mediated m6A Epitranscriptomics Drives CD80-Dependent Tubular Dysfunction in Sepsis-Induced AKI

Area of Science:

• Molecular Biology
• Cell Biology
• Renal Physiology

Background:

• Sepsis-associated acute kidney injury (S-AKI) involves renal tubular cell apoptosis and cytoskeletal abnormalities.
• The role of m6A modification-dependent proteins in S-AKI pathogenesis is not fully understood.

Purpose of the Study:

• To investigate the function of HNRNPC in S-AKI.
• To elucidate the molecular mechanisms linking HNRNPC, m6A modification, NF-κB signaling, and CD80 in S-AKI.

Main Methods:

• Dot blot, cell viability assays, flow cytometry, fluorescent phalloidin staining.
• RNA sequencing, luciferase reporter assays, Western blot, EMSA, ChIP assays.
• MeRIP-qPCR, RNA m6A quantification, in vivo experiments.

Main Results:

• HNRNPC induces renal tubular cell apoptosis and cytoskeletal damage in S-AKI.
• HNRNPC promotes CD80 expression transcriptionally via m6A-dependent NF-κB regulation.
• CD80 is crucial for HNRNPC-induced tubular injury.

Conclusions:

• HNRNPC plays a key role in S-AKI pathogenesis by regulating apoptosis and cytoskeleton.
• The HNRNPC/m6A/NF-κB/CD80 axis is a critical pathway in S-AKI.
• HNRNPC and CD80 represent potential therapeutic targets for S-AKI treatment.