Related Experiment Video

Updated: Sep 19, 2025

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
07:15

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

552

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

Jie Chen1, Libin Zou2, Lu Liu3

  • 1Department of Nephrology, Wuhan Third Hospital, Wuhan, Hubei Province, China.

Organogenesis
|June 17, 2025
PubMed

Insights

Orosomucoid 1 (ORM1) upregulation exacerbates podocyte injury in lupus nephritis (LN). Reducing ORM1 protects podocytes by modulating autophagy via the AMPK/mTOR pathway, offering a potential therapeutic strategy for LN.

Area of Science:

  • Nephrology
  • Immunology
  • Cell Biology

Background:

  • Podocyte damage is a key factor in lupus nephritis (LN) pathogenesis.
  • Identifying therapeutic targets to protect podocytes is crucial for improving LN treatment outcomes.
  • Orosomucoid 1 (ORM1) has emerged as a potential candidate gene implicated in LN.

Purpose of the Study:

  • To investigate the role of ORM1 in podocyte injury in a lupus nephritis model.
  • To explore the effects of ORM1 knockdown on podocyte viability, apoptosis, and autophagy.
  • To elucidate the involvement of the AMPK/mTOR signaling pathway in ORM1-mediated podocyte damage.

Main Methods:

  • Established a lupus nephritis (LN) model using mouse podocytes stimulated with patient-derived Immunoglobulin G (IgG).
  • Performed ORM1 knockdown and assessed podocyte viability (CCK-8 assay) and apoptosis (flow cytometry).
  • Analyzed autophagy markers (LC3II/I, p62) via western blotting/immunofluorescence and evaluated AMPK/mTOR pathway activation.

Main Results:

  • ORM1 expression was upregulated in the LN model.
  • ORM1 knockdown mitigated IgG-induced podocyte damage, reducing apoptosis and normalizing viability.
  • ORM1 knockdown decreased elevated autophagy levels and modulated AMPK/mTOR signaling (increased p-AMPK, decreased p-mTOR).

Conclusions:

  • ORM1 plays a significant role in podocyte injury within the lupus nephritis model.
  • ORM1 influences podocyte autophagy through the AMPK/mTOR signaling pathway.
  • Targeting ORM1 may represent a novel therapeutic approach for managing lupus nephritis.
Keywords:
AMPK/mTORORM1autophagylupus nephritispodocytes

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