MARCHF8-mediated ubiquitination via TGFBI regulates NF-κB dependent inflammatory responses and ECM degradation in intervertebral disc degeneration
2025

TGFBI's Role in Intervertebral Disc Degeneration

Sample size: 10 publication 20 minutes Evidence: moderate

Author Information

Author(s): Zhang Xingpeng, Li Guang, Tan Fang, Yu Tao, Xu Chengping, Li Kai, Zhang Feng, Zhang Meiyan, Wang Jian

Primary Institution: Department of Orthopedics, Shanghai Pudong New Area People’s Hospital, Shanghai, China

Hypothesis

To explore the role of the hub gene Transforming Growth Factor Beta Induced (TGFBI) in Intervertebral disc degeneration (IDD) pathogenesis and its regulatory relationship with Membrane Associated Ring-CH-Type Finger 8 (MARCHF8).

Conclusion

TGFBI, modulated by MARCHF8, significantly influences IDD progression by affecting NP cell apoptosis, ECM degradation, and inflammation through the NF-κB signaling pathway.

Supporting Evidence

  • WGCNA linked the MEturquoise module with IDD samples, revealing 145 shared genes among DEGs.
  • In vitro findings indicated that MARCHF8 determines TGFBI expression.
  • TGFBI boosts apoptosis and ECM breakdown in LPS-stimulated NP cells.
  • Altering TGFBI levels modulated these effects and the NF-κB signaling pathway.
  • MARCHF8 ubiquitination controlled TGFBI expression.

Takeaway

This study found that a protein called TGFBI helps control inflammation and cell death in a part of the spine that can get damaged, and another protein, MARCHF8, helps regulate TGFBI.

Methodology

The study used bioinformatics analysis on the GSE146904 dataset, WGCNA for key module identification, and in vitro experiments to explore the effects of TGFBI and MARCHF8 on NP cells.

Limitations

The in vitro nature of the experiments necessitates further validation in in vivo models to fully understand the systemic effects and potential side effects of modulating these proteins.

Participant Demographics

10 cases of soft NP samples of lumbar intervertebral disc, including 5 cases each of disc herniation and disc degeneration.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0314021

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