Identification of Key Genes Associated With Epithelial Barrier Dysfunction by Comprehensive Analysis and Experimental...

Area of Science:

• Immunology
• Molecular Biology
• Genetics

Background:

• Epithelial barrier dysfunction is a key feature in asthma, atopic dermatitis (AD), and ulcerative colitis (UC).
• Shared regulatory mechanisms underlying epithelial barrier dysfunction across these inflammatory conditions remain unclear.

Purpose of the Study:

• To identify common molecular mechanisms and key genes involved in epithelial barrier dysfunction across asthma, AD, and UC.
• To investigate the role of identified key genes in epithelial barrier integrity and their association with asthma clinical features.

Main Methods:

• Analysis of gene expression profiles from patients with asthma, AD, and UC.
• Identification of common differentially expressed genes (DEGs) and correlation with junction molecules.
• Construction of interaction networks and assessment of key genes' effects on epithelial barrier function in vitro.

Main Results:

• Eight common DEGs were upregulated across all three diseases; four key genes (CDC7, PXDN, TCN1, TIMP1) were identified.
• These key genes were upregulated in disease epithelia, elevated in IL-13-stimulated cells, and negatively correlated with junction molecules.
• Targeting CDC7 and TCN1 alleviated IL-13-induced barrier disruption in airway, epidermal, and intestinal epithelial cells.

Conclusions:

• CDC7 and TCN1 are identified as key regulators of epithelial barrier function.
• Targeting CDC7 and TCN1 offers a promising therapeutic strategy for diseases with epithelial barrier dysfunction.