ORM1 Mediates Ln-IgG-Induced Podocyte Damage and Autophagy via the AMPK/mTOR Signaling

PMCID: PMC12184165

PMID: 40526157

DOI: 10.1080/15476278.2025.2519614

Journal: Organogenesis

Publication Date: 2025-6-17

Authors: Chen J, Zou L, Liu L, Wu C, Hu M

Key Points

• ORM1 plays a critical role in podocyte damage and autophagy in lupus nephritis
• ORM1 knockdown increased podocyte viability by approximately 40% and reduced apoptosis rates
• Potential therapeutic strategy for mitigating renal damage in lupus nephritis by modulating ORM1 expression

Summary

This preclinical study investigated the role of ORM1 in podocyte damage associated with lupus nephritis (LN), a severe manifestation of systemic lupus erythematosus that significantly impacts renal function. Using an in vitro model with IgG from lupus patients, researchers explored how ORM1 modulates podocyte injury through autophagy and the AMPK/mTOR signaling pathway. The study demonstrated that ORM1 knockdown can mitigate podocyte damage by reducing apoptosis, decreasing autophagy levels, and modulating key cellular signaling mechanisms.

The research provides important insights into the molecular pathogenesis of lupus nephritis, highlighting ORM1 as a potential therapeutic target. By showing that ORM1 knockdown can protect podocytes from IgG-induced injury, the study offers a novel perspective on managing renal complications in lupus patients. The findings suggest that targeting ORM1 could potentially interrupt the pathological processes that lead to progressive kidney damage in lupus nephritis.