Proteomic Differences in Colonic Epithelial Cells in Ulcerative Colitis Have an Epigenetic Basis.

Area of Science:

• Gastroenterology
• Molecular Biology
• Epigenetics

Background:

• Ulcerative colitis (UC) is characterized by epithelial dysfunction.
• Cellular changes underlying UC pathology remain poorly understood.
• Investigating epithelial cell epigenetics and proteome in UC is crucial.

Purpose of the Study:

• To compare the chromatin epigenetics and proteome of colonic epithelial cells in healthy controls (HC) and UC patients.
• To identify cellular differences that may contribute to UC pathogenesis.
• To explore potential epigenetic mechanisms regulating these differences.

Main Methods:

• Sorted live CD326+ epithelial cells from colon biopsies of HC and UC patients.
• Analyzed cell lysates for proteomic evaluation.
• Assessed open chromatin using assay for transposase-accessible chromatin using sequencing (ATAC-seq).

Main Results:

• Elevated proteins in inflamed UC biopsies include HLA-DRA, CD74, DUOX2, and lipocalin-2.
• Reduced aquaporin 8 levels were observed in inflamed UC colonic epithelium.
• ATAC-seq revealed altered chromatin accessibility around aquaporin 8 and DUOX2/DUOXA2 loci.

Conclusions:

• Significant differences exist in the proteome and chromatin epigenetics of colonic epithelial cells between UC patients and HC.
• Findings suggest specific epigenetic mechanisms regulate epithelial cell proteome in UC.
• These cellular changes may underlie the pathology of ulcerative colitis.