Fig. 7: In vitro overexpression of E-cadherin or by activating the Nrf2 pathway protects E-cadherin expression and restores epithelial function in COPD and cigarette smoke (CS) injured epithelia.
From: Loss of E-cadherin is causal to pathologic changes in chronic lung disease
COPD cells at 4 to 6 weeks ALI were transfected Ad-GFP-U6-h-CDH1 (CDH1) to overexpress E-cadherin or Ad-GFP (GFP) as control at 2 × 109 pfu. COPD cells transfected with Ad-CDH1 result in a increased epithelial resistance, b reduced cellular velocity of COPD cells, and c increased mRNA expression of CDH1. Overexpression of E-cadherin in COPD cells d–g increased mRNA expression of claudins—CLDN1, CLDN3, CLDN7, and CLDN8, h decreased mRNA expression of CLDN10, i increased mRNA expression of occludin (OCLN), j increased mRNA expression of tight junction protein 1 (TJP1), and k TJP2 was not altered. Data is expressed as median bars and generated from 4 to 12 transwells per condition from two donors. To induce the over-expression of E-cadherin in Cdh1 knock-in mice, mice tracheal epithelial cells (mTECs) were transfected with adeno-Cre (Ad5CMVCre-eGFP) at 2 × 109 pfu and were exposed to CS for 10 days. Overexpression of E-cadherin in mTECs protects against CS-induced epithelial functional phenotypes by l decreasing monolayer permeability, m decreasing the cellular velocity, and n protecting Cdh1 mRNA downregulation due to CS exposure. Data for l–m involves three to six transwells per condition. COPD cells treated with CDDO-Me restore epithelial function by o improving the epithelial resistance, p decreasing the cellular velocity, and q increasing the CDH1 mRNA expression of COPD cells as compared to age and gender-matched non-diseased epithelium (normal controls). Similarly, cigarette smoke (CS) exposed to healthy normal cells treated with CDDO-Me r restores epithelial resistance, s decreases cellular velocity, and t protects against CDH1 mRNA downregulation due to CS exposure. (Data for o–t is generated from 3 to 6 transwells from 2 donors). For the panels the same data for normal are used for a–k, and o–t in the figure. Data are expressed as median bars. Kruskal-Wallis test, followed by Dunn’s multiple comparison test was performed. P < 0.05 were considered statistically significant.
