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ANGPTL4 May Regulate the Crosstalk Between Intervertebral Disc Degeneration and Type 2 Diabetes Mellitus: A Combined

Yan Chen1, Han Du1, Xin Wang1

  • 1Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People's Republic of China.

Journal of Inflammation Research
|January 1, 2024
PubMed
Abstract

Insights

This study identified ANGPTL4 as a key gene linking intervertebral disc degeneration and type 2 diabetes. Understanding this shared genetic mechanism offers new therapeutic targets for both conditions.

Area of Science:

  • Genomics and Molecular Biology
  • Biomedical Research
  • Disease Mechanisms

Background:

  • Intervertebral disc degeneration (IVDD) and type 2 diabetes mellitus (T2DM) share a complex relationship.
  • The underlying molecular mechanisms connecting IVDD and T2DM remain largely unelucidated.
  • Identifying shared genetic factors is crucial for understanding disease crosstalk.

Purpose of the Study:

  • To explore shared gene signatures between intervertebral disc degeneration (IVDD) and type 2 diabetes mellitus (T2DM).
  • To identify potential molecular targets for regulating the crosstalk between these two conditions.

Main Methods:

  • Acquired gene expression profiles for IVDD and T2DM from the Gene Expression Omnibus database.
  • Utilized bioinformatics analyses including Gene Ontology (GO) enrichment, functional correlation, and network construction (TFs-mRNA-miRNA).
  • Validated findings through RNA sequencing and in vivo/in vitro experiments in rats.

Main Results:

  • Five hub genes (ANGPTL4, CCL2, CCN3, THBS2, INHBA) were identified as potential shared signatures.
  • GO analysis indicated involvement in immune system regulation, extracellular matrix (ECM) processes, and SMAD signaling.
  • ANGPTL4 was confirmed as a key target gene, involved in inhibiting lipoprotein lipase activity, with significant validation.

Conclusions:

  • ANGPTL4 is identified as a potential key regulatory target in the crosstalk between IVDD and T2DM.
  • The study provides a foundation for understanding the shared genetic basis of these interconnected diseases.
  • Findings suggest ANGPTL4 as a promising therapeutic target for managing patients with both IVDD and T2DM.
Keywords:
ANGPTL4biomarkerfunctional analysisintervertebral disc degenerationtype 2 diabetes mellitus

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