Bruton tyrosine kinase (BTK) may be a potential therapeutic target for interstitial cystitis/bladder pain syndrome

Aging (Albany NY). 2022 Sep 5;14(17):7052-7064. doi: 10.18632/aging.204271. Epub 2022 Sep 5.

Abstract

Aims: To determine the potential diagnostic and therapeutic targets of Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS).

Methods: We selected the GSE11783, GSE57560 and GSE621 datasets from the GEO database and merged them. R software was used to screen differentially expressed genes (DEGs) between IC/BPS and normal bladder tissues. The "String" online tool is used to analyze DEGs interaction and functional protein enrichment. CIBERSORT online tool was used to analyze the infiltration of immune cells. In addition, we verified the function of BTK in IC/BPS at the clinical samples and cells level.

Results: Bioinformatics analysis revealed that 5 genes were significantly overexpressed in IC/BPS, and the protein-protein interaction diagram showed that BTK was a critical link between these five proteins. At the same time, functional enrichment showed that they were significantly related to innate immunity. Immunoinfiltration showed that mast cell resting in IC/BPS was significantly higher. IHC staining of clinical samples showed that the mast cell markers Tryptase and BTK were highly expressed in IC/BPS tissues. At the cell level, knockdown of BTK inhibited proliferation, migration, invasion, and degranulation of mast cells.

Conclusions: This study provides a new perspective for understanding the molecular mechanisms involved in IC/BPS and suggests that BTK may be a target for treating IC/BPS.

Keywords: BTK; bioinformatics; biomarker; interstitial cystitis; mast cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase / genetics
  • Cystitis, Interstitial* / diagnosis
  • Cystitis, Interstitial* / genetics
  • Humans
  • Mast Cells
  • Tryptases
  • Urinary Bladder

Substances

  • Agammaglobulinaemia Tyrosine Kinase
  • Tryptases