📚 Wiki Tissue Repair Trefoil Factor 1

Trefoil Factor 1

○ Phase I
Page last reviewed

Quick Summary

6 kDa secreted peptide produced predominantly by gastric pit mucous cells. It contains a single trefoil domain (three-leaf clover-shaped disulfide fold) that confers protease resistance and gel-forming properties.

Trefoil factor 1 (TFF1) is a 6.6 kDa secreted peptide produced predominantly by gastric pit mucous cells. It contains a single trefoil domain (three-leaf clover-shaped disulfide fold) that confers protease resistance and gel-forming properties. TFF1 protects gastric mucosa, promotes epithelial restitution after injury, and its expression is markedly elevated in response to ulcerogenic insults.
Storage Stability
Lyophilized
~1 year
Reconstituted
N/A (oral)
Room temp
Stable (capsule)
Trefoil factor 1 (TFF1) is a 6.6 kDa secreted peptide produced predominantly by gastric pit mucous cells. It contains a single trefoil domain (three-leaf clover-shaped disulfide fold) that confers protease resistance and gel-forming properties. TFF1 protects gastric mucosa, promotes epithelial restitution after injury, and its expression is markedly elevated in response to ulcerogenic insults.

Mechanism of Action

  • Stabilizes mucin gels by non-covalent interaction with MUC5AC, enhancing the viscous protective layer over gastric epithelium
  • Promotes epithelial cell migration (restitution) into wounded areas via activation of focal adhesion kinase (FAK) and RhoA/ROCK pathways
  • Stimulates EGF receptor transactivation in gastric cells, triggering ERK1/2 and PI3K/Akt survival signaling
  • Inhibits anoikis (anchorage-independent apoptosis) in gastric epithelial cells during restitution
  • Anti-apoptotic: TFF1 protects cells from NSAID-induced and H. pylori-induced mucosal damage

Research Findings

  • TFF1 knockout mice spontaneously develop antral gastric adenomas and carcinomas by 3-6 months, establishing its tumor-suppressor role
  • TFF1 administered intragastrically or IV accelerates healing of acetic acid-induced gastric ulcers in rats
  • TFF1 levels markedly reduced in gastric adenocarcinoma vs surrounding normal mucosa; loss correlates with poor prognosis
  • Estrogen strongly induces TFF1 in breast tissue (the original pS2 discovery); breast cancer TFF1 expression marks hormone-responsive tumors
  • TFF1 nasal administration explored as cytoprotectant in radiation-induced oral mucositis in Phase I/II trials

Research Protocols

  • Recombinant TFF1: 50-200 ng/mL on gastric epithelial cell monolayers for migration/wound healing assays
  • Rat ulcer model: 50-200 mcg/kg IV or IG twice daily for 7 days during ulcer healing studies
  • Intranasal TFF1 (TeloVac/SBG) for oral mucositis: 0.5-2 mg/day topical rinse in Phase I patients
  • TFF1 IHC/ELISA: standard diagnostic use to assess gastric cancer hormone sensitivity and prognosis

Interactions

  • MUC5AC mucin: physical interaction in gastric mucus layer; synergistic mucosal protection
  • EGF and EGF receptor: TFF1 synergizes with EGF in epithelial migration and proliferation
  • H. pylori: TFF1 upregulated in response to infection; H. pylori urease may cleave TFF1 in severe infection

Safety Profile

Endogenous protective peptide. No significant adverse effects observed in animal studies or early clinical mucositis trials. Potential concern: TFF1 paradoxically promotes invasion in established gastric carcinoma cells via CXCR4 signaling despite being a tumor suppressor in normal tissue.

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Verified Scientific Data Last audited:
Data Sources & External References
Source: peer-reviewed literature  ·  Domain: ascendpeptide.org

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