Role of TGF-Beta and Smad7 in Gut Inflammation, Fibrosis and Cancer

• Published in: Biomolecules (Basel, Switzerland) Vol. 11; no. 1; p. 17
• Main Authors: Stolfi, Carmine, Troncone, Edoardo, Marafini, Irene, Monteleone, Giovanni
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27.12.2020; MDPI
• Subjects: Antigens; Colon cancer; Colorectal cancer; Crohn’s disease; Cytokines; Digestive system; Digestive tract; Epithelial cells; epithelial-mesenchymal transition; Fibrosis; Gastric cancer; Gastrointestinal tract; Homeostasis; Immune response; Immune system; Immunological tolerance; Inflammation; Inflammatory bowel diseases; Intestine; Kinases; Leukocytes; Lymphocytes; Microbiota; Mucosal immunity; Phosphorylation; Production increases; Review; Smad7 protein; Stromal cells; Transcription factors; Transforming growth factor-b1; colorectal cancer; TNF-α; gastric cancer; inflammatory bowel diseases; antisense oligonucleotides; cytokines; epithelial-mesenchymal transition; Crohn’s disease; Th17 cells; mucosal immunity
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom11010017

The human gastrointestinal tract contains the largest population of immune cells in the body and this is a reflection of the fact that it is continuously exposed to a myriad of dietary and bacterial antigens. Although these cells produce a variety of inflammatory cytokines that could potentially promote tissue damage, in normal conditions the mucosal immune response is tightly controlled by counter-regulatory factors, which help induce and maintain gut homeostasis and tolerance. One such factor is transforming growth factor (TGF)-β1, a cytokine produced by multiple lineages of leukocytes, stromal cells and epithelial cells, and virtually targets all the gut mucosal cell types. Indeed, studies in animals and humans have shown that defects in TGF-β1 production and/or signaling can lead to the development of immune-inflammatory pathologies, fibrosis and cancer in the gut. Here, we review and discuss the available evidence about the role of TGF-β1 and Smad7, an inhibitor of TGF-β1 activity, in gut inflammation, fibrosis and cancer with particular regard to the contribution of these two molecules in the pathogenesis of inflammatory bowel diseases and colon cancer.