Daily Archives: February 8, 2019

It is well-established that microbiota and immune cells signal to colon epithelial cells to increase production of chemokines and pro-inflammatory cytokines that can accelerate inflammation, but we have found that TGFβ/SMAD4 signaling in colon epithel… Continue reading →

The complex inflammatory bowel diseases, Crohn’s Disease (CD) and Ulcerative Colitis (UC), are driven by a myriad of immune, microbial, and environmental factors that manifest in tissue inflammation and lesions. Though several mouse models exist for … Continue reading →

Melanin concentrating hormone (MCH) was first identified as a hypothalamic neuropeptide regulating feeding behavior and energy balance. The MCH receptor, MCHR1, is present in brain as well as in several peripheral tissues including the gastrointestinal… Continue reading →

biological therapies such as anti tumor necrosis factor α (TNFα) drug infliximab (IFX), have led to substantial improvements in the treatment of Crohn’s disease (CD) patients. However, approximately a third of them do not have a response during ind… Continue reading →

Previous studies revealed both genetic and environmental factors contribute to the Crohn’s disease pathogenesis. ATG16L1, an essential component of autophagy, is one of the susceptibility genes of the disease. We previously showed that mice with decr… Continue reading →

IL-17A, derived from Th17 cells, plays an important role in intestinal host defense. However, the interaction and potential molecular synergies between IL-17A and epithelial cell lineages, intestinal stem cells (ISCs), and progenitors of the intestine … Continue reading →

Fibrostenosis complicates Crohn’s disease in the 30-50% of patients with a Montreal B2 phenotype. Current medical therapies can delay but no prevent critical fibrostenosis and the need for surgery. Transforming growth factor-β1 (TGF-β1)-induced exc… Continue reading →

Epithelial cells migrate and proliferate to cover denuded mucosal surfaces. The intestinal mucosal infiltrating immune cells and epithelium secrete an array of inflammatory mediators that have been proposed to modulate wound repair. Here, we report tha… Continue reading →

Progressive tissue remodeling characterized by extensive collagen production and excess extracellular matrix deposition leads to intestinal fibrosis and stricture formation in patients with fibrostenotic Crohn’s disease. Currently medical therapies c… Continue reading →

Genome-wide association studies (GWAS) have identified >200 risk loci in Crohn’s disease and ulcerative colitis or as shared loci. Pathway analysis of these risk loci identified several variants in the Jak-STAT candidate network and of protein tyrosine phosphatase non-receptor type 2 (PTPN2, TC-PTP). PTPN2 dephosphorylates not only receptor protein tyrosine kinases but also non-receptor protein tyrosine kinases like JAK1, JAK2, JAK3, the Src family kinases, STAT3. In subepithelial myofibroblasts from strictured ileum of patient with fibrostenotic Crohn’s disease we identified a unique signaling pathway, of JAK-mediated STAT3(S727) and STAT3(Y705) phosphorylation regulated increased TGF-β1 expression and increased collagen I production. Continue reading →