{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTMIGD1 is a conserved transmembrane and immunoglobulin domain–containing adhesion molecule predominantly expressed in renal tubular and intestinal epithelial cells. In renal epithelial cells, TMIGD1 regulates barrier functions by modulating transepithelial electrical resistance, cell morphology, and migration, and it confers protection against oxidative and nutrient deprivation–induced injury. Notably, its expression is downregulated under oxidative conditions via ubiquitination, consistent with a protective role in maintaining cell viability and epithelial integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the intestine, TMIGD1 is enriched in the apical microvilli of well‐differentiated enterocytes and appears to play an important role in epithelial differentiation and mucosal recovery. Transcriptomic analyses in Crohn’s disease patients have revealed pronounced underexpression of TMIGD1, particularly in inflamed tissue, implicating it in cell recovery and tissue remodeling processes in response to inflammatory insults."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurther supporting its functional importance, TMIGD1 has emerged as a tumor suppressor in the gastrointestinal tract. In mouse models, loss of TMIGD1 leads to the development of adenomas in both the small intestine and colon, accompanied by impaired brush border formation, altered junctional polarity, and disrupted epithelial maturation. In human colorectal cancer, TMIGD1 is significantly downregulated, and its reduced expression correlates with enhanced cell proliferation, migration, and poorer overall patient survival. Mechanistic studies indicate that TMIGD1 attenuates tumorigenesis by arresting cell cycle progression at the G2/M phase and upregulating cyclin-dependent kinase inhibitors such as p21CIP1 and p27KIP1, with overexpression experiments confirming its ability to restrain metastasis and tumor growth in vivo."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Emad Arafa, Philip A Bondzie, Kobra Rezazadeh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMIGD1 is a novel adhesion molecule that protects epithelial cells from oxidative cell injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajpath.2015.06.006"}], "href": "https://doi.org/10.1016/j.ajpath.2015.06.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26342724"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26342724"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Christian Hartmann, Ysabel Alessa Schwietzer, Daniel Kummer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The mitochondrial outer membrane protein SYNJ2BP interacts with the cell adhesion molecule TMIGD1 and can recruit it to mitochondria."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Mol Cell Biol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12860-020-00274-1"}], "href": "https://doi.org/10.1186/s12860-020-00274-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32303178"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32303178"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yamile Zabana, Violeta Lorén, Eugeni Domènech, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcriptomic identification of TMIGD1 and its relationship with the ileal epithelial cell differentiation in Crohn's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Gastrointest Liver Physiol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpgi.00027.2020"}], "href": "https://doi.org/10.1152/ajpgi.00027.2020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32508154"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32508154"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Kyle O C De La Cena, Rachel X-Y Ho, Razie Amraei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transmembrane and Immunoglobulin Domain Containing 1, a Putative Tumor Suppressor, Induces G2/M Cell Cycle Checkpoint Arrest in Colon Cancer Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajpath.2020.09.015"}], "href": "https://doi.org/10.1016/j.ajpath.2020.09.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33129760"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33129760"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Lijun Mu, Yue Wang, Yuan Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Role of TMIGD1 as a Tumor Suppressor in Colorectal Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genet Test Mol Biomarkers (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/gtmb.2021.0169"}], "href": "https://doi.org/10.1089/gtmb.2021.0169"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35481970"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35481970"}]}]}]}