Mucosal Healing Pathway

Preferred Label : Mucosal Healing Pathway;

NCIt related terms : Trefoil Factors Initiate Mucosal Healing;

Alternative definition : BIOCARTA: Maintaining the integrity of the gastrointestinal tract despite the continual presence of microbial flora and injurious agents is essential. Epithelial repair requires restitution and regeneration. During restitution, epithelial cells spread and migrate across the basement membrane to re-establish surface-cell continuity, a process that is independent of cell proliferation. Epithelial continuity depends on a family of small abundant secreted proteins, the trefoil factors (TFFs). The trefoil factor (TFF) family comprises the gastric peptides pS2/TFF1 and spasmolytic peptide (SP)/TFF2, and the intestinal trefoil factor (ITF)/TFF3. Their fundamental action is to promote epithelial-cell restitution within the gastrointestinal tract. TFFs are abundantly secreted onto the mucosal surface by mucus-secreting cells. Their expression is rapidly and coordinately upregulated at the margins of mucosal injury. Secreted TFF acts on adjacent mucosal cell populations either extracellularly (augmenting barrier function) or intracellularly (transcriptional and signaling events). TFF response elements in TFF gene promoters allow increases in TFF expression through auto-induction and cross-induction of other TFFs, in addition to mucin expression and possibly tumor suppression. Cell migration is the result of integrated disruption of cell-cell and cell-substratum adhesion and prevention of apoptosis through cell detachment. Epithelial movement therefore requires integration of motogenic and cell-survival signals. This is achieved by activation of several intracellular signaling pathways that converge on ERK/MAPK and possibly NF-B activation. Serine phosphorylation of the extracellular signal-regulated kinases (ERKs)/mitogen-activated protein kinases (MAPKs) 1 and 2 is central to trefoil factor-mediated signaling, lying downstream of EGFR activation and possibly FAK activation (through recruitment of GRB2 and SOS). Cell migration might result from cooperation between ERK/MAPKs and Rho proteins, FAK activation, beta-integrin clustering and beta-catenin activation. Abrogation of cell death has been shown to require both PI3K activation and ERK/MAPK activation; the former operates through serine/threonine phosphorylation of AKT/protein kinase B, serine phosphorylation of BAD (BCL-2 agonist of cell death) and inhibition of mitochondrial cytochrome c release and formation of the apoptosome (APAF1, caspase-9 (CASP9) and cytochrome c (CYT-c). Translocation of phosphorylated ERK/MAPK to the nucleus leads to amplification and de-restriction of TFF expression to ensure sustained action. (This definition may be outdated - see the DesignNote.);

NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA Definition might be outdated or inaccurate. Please see the Terms and Conditions for Use at http://www.biocarta.com/.;

Biocarta ID : h_tffPathway;

Details

Origin ID

C39250;

UMLS CUI

C1513724;

Semantic type(s)
- Organ or Tissue Function [UMLS semantic type]
has_gene_product_element
- 3-Phosphoinositide-Dependent Protein Kinase 1 [NCIt concept]
- Activated Caspase-9 [NCIt concept]
- Apoptotic Protease-Activating Factor 1 [NCIt concept]
- Bcl2 Antagonist of Cell Death [NCIt concept]
- Caspase-3 [NCIt concept]
- Caspase-6 [NCIt concept]
- Caspase-9 [NCIt concept]
- Catenin Beta-1 [NCIt concept]
- Dual Specificity Mitogen-Activated Protein Kinase Kinase 2 [NCIt concept]
- Epidermal Growth Factor Receptor [NCIt concept]
- Focal Adhesion Kinase 1 [NCIt concept]
- GTPase HRas [NCIt concept]
- Growth Factor Receptor-Bound Protein 2 [NCIt concept]
- Growth Hormone Receptor [NCIt concept]
- Mitogen-Activated Protein Kinase 1 [NCIt concept]
- Mitogen-Activated Protein Kinase 3 [NCIt concept]
- Mucin-2 [NCIt concept]
- NF-Kappa-B Inhibitor Alpha [NCIt concept]
- Phosphatidylinositol 3-Kinase Regulatory Subunit Alpha [NCIt concept]
- Phosphatidylinositol 4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha Isoform [NCIt concept]
- Phosphatidylinositol 4,5-Bisphosphate 3-Kinase Catalytic Subunit Gamma Isoform [NCIt concept]
- RAC-Alpha Serine/Threonine Kinase [NCIt concept]
- Receptor Tyrosine-Protein Kinase erbB-2 [NCIt concept]
- SHC-Transforming Protein 1 [NCIt concept]
- Somatotropin [NCIt concept]
- Son of Sevenless Homolog 1 [NCIt concept]
- Transcription Factor p65 [NCIt concept]
- Transforming Protein RhoA [NCIt concept]
- Trefoil Factor 3 [NCIt concept]
pathway_has_gene_element
- AKT1 wt Allele [NCIt concept]
- APAF1 wt Allele [NCIt concept]
- BAD wt Allele [NCIt concept]
- CASP3 wt Allele [NCIt concept]
- CASP6 wt Allele [NCIt concept]
- CASP9 wt Allele [NCIt concept]
- CTNNB1 wt Allele [NCIt concept]
- EGFR wt Allele [NCIt concept]
- ERBB2 wt Allele [NCIt concept]
- GH1 wt Allele [NCIt concept]
- GHR wt Allele [NCIt concept]
- GRB2 wt Allele [NCIt concept]
- HRAS wt Allele [NCIt concept]
- MAP2K2 wt Allele [NCIt concept]
- MAPK1 wt Allele [NCIt concept]
- MAPK3 wt Allele [NCIt concept]
- MUC2 wt Allele [NCIt concept]
- NFKBIA wt Allele [NCIt concept]
- PIK3CA wt Allele [NCIt concept]
- PIK3CG wt Allele [NCIt concept]
- PIK3R1 wt Allele [NCIt concept]
- PTK2 wt Allele [NCIt concept]
- RELA wt Allele [NCIt concept]
- RHOA wt Allele [NCIt concept]
- SHC1 wt Allele [NCIt concept]
- SOS1 wt Allele [NCIt concept]
- TFF3 wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

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