Studies have indicated that the HMGB1/RAGE signaling pathway downregulates the expression of VE-cadherin and E-cadherin in endothelium and epithelium, respectively, paralleled with decreased expression of TJs proteins such as occludins, claudins and ZO-1 in preclinical ARDS models (Fig. 3) [67, 171]. The gene discussed is HMGB1; the disease is acute respiratory distress syndrome.