RGD Reference Report - Altered expression of Tumor Necrosis Factor Alpha -Induced Protein 3 correlates with disease severity in Ulcerative Colitis. - Rat Genome Database

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Altered expression of Tumor Necrosis Factor Alpha -Induced Protein 3 correlates with disease severity in Ulcerative Colitis.

Authors: Majumdar, Ishani  Ahuja, Vineet  Paul, Jaishree 
Citation: Majumdar I, etal., Sci Rep. 2017 Aug 25;7(1):9420. doi: 10.1038/s41598-017-09796-9.
RGD ID: 151347619
Pubmed: PMID:28842689   (View Abstract at PubMed)
PMCID: PMC5572729   (View Article at PubMed Central)
DOI: DOI:10.1038/s41598-017-09796-9   (Journal Full-text)

Ulcerative colitis (UC), an inflammatory disorder of the colon arises from dysregulated immune response towards gut microbes. Transcription factor NFκB is a major regulatory component influencing mucosal inflammation. We evaluated expression of Tumor Necrosis Factor Alpha Induced Protein3 (TNFAIP3), the inhibitor of NFκB activation and its associated partners ITCH, RNF11 and Tax1BP1 in inflamed mucosa of UC patients. We found highly significant up-regulated mRNA expression of TNFAIP3 that negatively correlated with disease activity in UC. mRNA levels of ITCH, RNF11 and Tax1BP1 were significantly down-regulated. Significant positive correlation with disease activity was noted for Tax1BP1. All four genes showed significant down-regulation at protein level. mRNA levels of inducers of TNFAIP3 expression, NFκB p65 subunit and MAST3 was determined. There was significant increase in p65 mRNA expression and down-regulated MAST3 expression. This suggested that increase in NFκB expression regulates TNFAIP3 levels. Deficiency of TNFAIP3 expression resulted in significant up-regulation of NFκB p65 sub-unit as well as its downstream genes such as iNOS, an inflammatory marker, inhibitors of apoptosis like cIAP2 and XIAP and mediators of anti-apoptotic signals TRAF1 and TRAF2. Taken together, decreased expression of TNFAIP3 and its partners contribute to inflammation and up-regulation of apoptosis inhibitors that may create microenvironment for colorectal cancer.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
ulcerative colitis severityIEP 151347619mRNA more ...RGD 
ulcerative colitis severityISOTNFAIP3 (Homo sapiens)151347619; 151347619mRNA more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tnfaip3  (TNF alpha induced protein 3)

Genes (Mus musculus)
Tnfaip3  (tumor necrosis factor, alpha-induced protein 3)

Genes (Homo sapiens)
TNFAIP3  (TNF alpha induced protein 3)


Additional Information