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

TL;DR

This study shows that ORM1 contributes to kidney cell damage in lupus nephritis by affecting cell survival and autophagy through a specific signaling pathway.

Contribution

The study identifies ORM1 as a novel modulator of podocyte damage via the AMPK/mTOR signaling pathway in lupus nephritis.

Findings

ORM1 knockdown improved podocyte viability and reduced apoptosis in a lupus nephritis model.

ORM1 knockdown decreased autophagy levels and altered AMPK/mTOR signaling in podocytes.

ORM1 appears to mediate podocyte damage through AMPK/mTOR pathway modulation.

Abstract

Podocyte damage is a central feature of lupus nephritis (LN), making the identification of potential therapeutic targets to prevent podocyte injury and improve treatment outcomes essential. ORM1 has been suggested as a significant candidate gene in LN. In this study, mouse podocytes were induced using Immunoglobulin G (IgG) extracted from lupus patients. To investigate the role of ORM1, ORM1 knockdown was performed, and the effects on podocyte viability and apoptosis were assessed using the cell counting kit-8 (CCK-8) assay and flow cytometry. Additionally, autophagy markers LC3II/I and p62 were measured by western blotting and immunofluorescence, and the expression of the AMPK/mTOR signaling pathway was evaluated using western blotting. The results showed an upregulation of ORM1 in the LN model. Upon stimulation with IgG from LN patients, ORM1 knockdown reversed the reduction in podocyte viability, decreased the apoptosis rate, and reduced the elevated levels of autophagy, followed by an increase in AMPK phosphorylation and a decrease in mTOR phosphorylation. In conclusion, these results suggest that ORM1 modulates the expression of autophagy-related components in podocytes through the AMPK/mTOR signaling pathway, thereby influencing podocyte damage in the LN model in vitro.

Figures