Study on the role of calcium channel protein TRPV4 in the inflammatory pathway of type 2 diabetic adipose tissue based on gene databases

Biochem Biophys Res Commun. 2023 Jan 8:639:161-168. doi: 10.1016/j.bbrc.2022.11.078. Epub 2022 Nov 26.

Abstract

Background: Chronic inflammation of adipose tissue may be one of the key factors contributing to the development of insulin resistance in T2DM adipose tissue. Transient receptor potential vanilloid type 4 (TRPV4) can be involved in a variety of cellular inflammatory responses. In this study, we evaluated the role of TRPV4 channelin in the T2DM adipose tissue inflammatory pathway.

Methods: Based on the gene expression profiling data of the public database, bioinformatics methods were used to screen the target gene population of the TRPV4 channel protein involved in the regulation of T2DM fat cells. A mature adipocyte model was constructed to verify the expression level of target genes and to evaluate the regulatory effect of TRPV4 channel inhibition on target genes of inflammation-related pathways.

Results: In shTRPV4 adipocytes, 144 genes with downregulation expression were screened, a PPI network was constructed and a core module containing 15 genes was screened out, and the core genes were mainly enriched in the Toll-like receptor signaling pathway through enrichment analysis. Constructing a mature adipocyte model found that the TRPV4 inhibitor HC067047 inhibited the effect of upregulation of the expression level of the relevant gene in the signaling pathway.

Conclusions: Our findings suggest that the expression of highly expressed pro-inflammatory cytokines and chemokines in T2DM adipose tissue decreases after inhibiting the expression of TRPV4 in adipocytes, suggesting that TRPV4 may become a potential drug target for the treatment of T2DM.

Keywords: Adipose tissue; Functional verification; Inflammation; TRPV4; Type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Calcium Channels*
  • Diabetes Mellitus, Type 2* / genetics
  • Diabetes Mellitus, Type 2* / metabolism
  • Humans
  • Inflammation / genetics
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism

Substances

  • Calcium Channels
  • TRPV Cation Channels
  • TRPV4 inhibitor HC067047
  • TRPV4 protein, human