Fig. 6

Selective ATF6 activator AA147 rescued PCDH20-deficiency-associated epithelial barrier impairment. a–f AA147 rescued severe colitis in Pcdh20 CKO mice after DSS administration. Weight loss (a), disease activity index (b), colon length (c,d), ulcers, pathology score (e), magnification × 100, scale bars = 50 μm), and myeloperoxidase (MPO) activity (f). g AA147 rescued elevated FD4 level in Pcdh20 CKO mice with DSS-induced colitis. h,i Ameliorated paracellular permeability in PCDH20-deficient Caco-2 cells transfected with ATF6 overexpression plasmids along with the treatment of TNFα (2.5 ng/mL), IFN-γ (10 ng/mL). Transepithelial electrical resistance (TEER) (h), paracellular permeability assessment with FD4 (i). j Immunoblots of CHOP and adherens junctions components in Pcdh20 CKO mice treated with AA147 in DSS colitis group. k,l PCDH20 regulated CHOP/β-catenin/p-p120-catenin (S288/T310) by targeting ATF6 in two cell lines treated with TNFα (2.5 ng/mL), IFN-γ (10 ng/mL). m Mechanism graph: PCDH20 protects against colitis by tightening adherens junctions partly through the ATF6/CHOP/β-catenin/p-p120-catenin axis. The data in a–i are presented as mean ± SEM. * p < 0.05, **p < 0.01, ***p < 0.001 vs Control