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Updated: Jun 19, 2026

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

Rab1a attenuates TNF-α-induced apoptosis and extracellular matrix degradation in nucleus pulposus cells by inhibiting

Shicheng Li1, Yuhui Wang2, Xianxu Zhang1

  • 1Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou 730030, China; Orthopedic Clinical Medical Research Center and Intelligent Orthopedic Industry Technology Center of Gansu Province, Lanzhou 730030, China.

International Immunopharmacology
|June 17, 2026
PubMed
Abstract

Insights

Rab1a, a protein, was found to be reduced in intervertebral disc degeneration (IVDD). Restoring Rab1a levels protected against IVDD by reducing cell death and extracellular matrix breakdown via the PI3K-Akt pathway.

Area of Science:

  • Biomedical Research
  • Molecular Biology
  • Cellular Biology

Background:

  • Intervertebral disc degeneration (IVDD) is a primary cause of low back pain, with limited effective molecular targets.
  • Understanding the molecular mechanisms underlying IVDD is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the role of Rab1a in the pathogenesis of IVDD.
  • To elucidate the regulatory mechanism of Rab1a in nucleus pulposus cells (NPCs).

Main Methods:

  • Assessed Rab1a expression in a rat IVDD model and TNF-α-induced NPCs.
  • Evaluated the therapeutic effect of Rab1a overexpression in vivo and in vitro, examining NPC apoptosis and extracellular matrix (ECM) metabolism.
  • Utilized transcriptome sequencing, Western blot, and pathway analysis to identify downstream targets, including the PI3K-Akt pathway.

Main Results:

  • Rab1a expression was significantly downregulated in degenerated tissues and NPCs.
  • Rab1a overexpression attenuated IVDD progression, reduced NPC apoptosis, and preserved ECM integrity in vivo and in vitro.
  • Knockdown of Rab1a exacerbated apoptosis and ECM degradation, effects reversed by PI3K inhibition and mimicked by Akt activation.

Conclusions:

  • Rab1a plays a protective role in IVDD by inhibiting excessive PI3K-Akt pathway activation.
  • Rab1a attenuates NPC apoptosis and ECM degradation, suggesting its potential as a therapeutic target for IVDD.
Keywords:
ApoptosisExtracellular matrixIntervertebral disc degenerationPI3K-Akt signaling pathwayRab1a

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