We reported that increased endoplasmic reticulum (ER) stress signaling in subepithelial myofibroblasts (SEMF) isolated from patients with stricturing Crohn’s disease contributes to activation of TGF-β1 and fibrosis. Increased TGF-β1 results from increased interaction between GRP78 and latent TGF-beta and their translocation to the cell membrane where latent TGF-β1 is activated by αVβ3 integrin. Inhibition of ER stress by miR-199a is also lost due to DNA methyltransferase-1 (DNMT1)-induced promoter silencing of miR-199a-5p.