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Trefoil Factor 3

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Quick Summary

Trefoil factor 3 (TFF3), also called intestinal trefoil factor (ITF), is the most abundantly expressed trefoil peptide in the small intestine and colon. It is produced by goblet cells throughout the intestinal epithelium and is critical for mucosal repair after injury, functioning both as a local autocrine/paracrine repair factor and as a luminal protector of the epithelial barrier.

Trefoil factor 3 (TFF3), also called intestinal trefoil factor (ITF), is the most abundantly expressed trefoil peptide in the small intestine and colon. It is produced by goblet cells throughout the intestinal epithelium and is critical for mucosal repair after injury, functioning both as a local autocrine/paracrine repair factor and as a luminal protector of the epithelial barrier.
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Storage Stability
Lyophilized
~1 year
Reconstituted
N/A (oral)
Room temp
Stable (capsule)
Trefoil factor 3 (TFF3), also called intestinal trefoil factor (ITF), is the most abundantly expressed trefoil peptide in the small intestine and colon. It is produced by goblet cells throughout the intestinal epithelium and is critical for mucosal repair after injury, functioning both as a local autocrine/paracrine repair factor and as a luminal protector of the epithelial barrier.

Mechanism of Action

  • Interacts with MUC2 mucin in intestinal goblet cell secretions, reinforcing the mucus gel barrier
  • Promotes rapid epithelial restitution (cell migration into wounded areas) within hours of injury via FAK/Src/PI3K activation
  • Anti-apoptotic: protects intestinal epithelial cells from cytokine-induced and irradiation-induced apoptosis via NF-kB pathway
  • Reduces intestinal permeability and tight junction disruption during inflammatory challenge
  • Stimulates goblet cell differentiation and mucin gene expression in intestinal progenitor cells

Research Findings

  • TFF3 knockout mice show dramatically impaired colonic mucosal healing after dextran sodium sulfate (DSS) colitis, with higher mortality
  • Recombinant TFF3 enema or oral administration reduced severity and accelerated healing in DSS colitis and TNBS colitis models
  • TFF3 levels markedly reduced in active inflammatory bowel disease (Crohn and ulcerative colitis) mucosa
  • TFF3 clinical trial (oral recombinant ITF): reduced gut permeability and diarrhea severity in AIDS enteropathy patients
  • TFF3 combined with oral rehydration solution (ORS) improved outcomes vs ORS alone in childhood diarrhea clinical trial

Research Protocols

  • DSS colitis mouse model: 0.5-5 mg/kg oral or rectal TFF3 daily for 7-14 days
  • Human clinical trials: oral recombinant TFF3 at 0.5-3 g/day (as luminal doses for IBD/AIDS enteropathy)
  • Enema: 50-200 mg recombinant TFF3 per enema for distal colitis in pilot studies
  • In vitro migration assay: 10-100 ng/mL TFF3 on Caco-2 or IEC-6 intestinal cell monolayer wound scratch

Interactions

  • MUC2: essential partner in intestinal mucus gel; TFF3 lost from mucus in goblet cell-depleted models
  • EGF receptor: TFF3 transactivates EGFR; EGFR inhibitors block TFF3-mediated migration
  • TNF-alpha and IL-1beta: TFF3 expression reduced by these cytokines during active IBD, impairing repair

Safety Profile

Well tolerated in animal and early clinical studies. Oral recombinant TFF3 at gram doses produced no significant systemic adverse effects. Potential concern: elevated serum TFF3 in some cancers (gastric, breast) may reflect escape from tumor suppression; therapeutic use targets mucosal not systemic doses.

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Categories: Endogenous PeptideMucosal ProtectantTrefoil Factor FamilyIntestinal BiologyIBD ResearchWound Healing
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Data Sources & External References
⬡ PubMed / NCBI, Research Literature ⬡ NCBI, Full-Text Articles ⬡ PubChem, Chemical Database
Source: peer-reviewed literature  ·  Domain: ascendpeptide.org

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