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

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.