Single-cell analysis identifies phospholysine phosphohistidine inorganic pyrophosphate phosphatase as a target in ulcerative colitis

World J Gastroenterol. 2023 Dec 28;29(48):6222-6234. doi: 10.3748/wjg.v29.i48.6222.

Abstract

Background: Ulcerative colitis (UC) is a chronic gastrointestinal disorder characterized by inflammation and ulceration, representing a significant predisposition to colorectal cancer. Recent advances in single-cell RNA sequencing (scRNA-seq) technology offer a promising avenue for dissecting the complex cellular inter-actions and molecular signatures driving UC pathology.

Aim: To utilize scRNA-seq technology to dissect the complex cellular interactions and molecular signatures that underlie UC pathology.

Methods: In this research, we integrated and analyzed the scRNA-seq data from UC patients. Moreover, we conducted mRNA and protein level assays as well as pathology-related staining tests on clinical patient samples.

Results: In this study, we identified the sustained upregulation of inflammatory response pathways during UC progression, characterized the features of damaged endo-thelial cells in colitis. Furthermore, we uncovered the downregulation of phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) has a negative correlation with signal transducer and activator of transcription 3. Significant downregulation of LHPP in UC patient tissues and plasma suggests that LHPP may serve as a potential therapeutic target for UC. This paper highlights the importance of LHPP as a potential key target in UC and unveils its potential role in inflammation regulation.

Conclusion: The findings suggest that LHPP may serve as a potential therapeutic target for UC, emphasizing its importance as a potential key target in UC and unveiling its role in inflammation regulation.

Keywords: Phospholysine phosphohistidine inorganic pyrophosphate phosphatase; Single-cell RNA sequencing; Ulcerative colitis.

MeSH terms

  • Colitis, Ulcerative* / genetics
  • Diphosphates
  • Humans
  • Inflammation
  • Phosphoric Monoester Hydrolases
  • Single-Cell Analysis

Substances

  • Diphosphates
  • phosphohistidine
  • Phosphoric Monoester Hydrolases