Description
Thymosin Beta-4 (TB-500) – Technical Biochemical Mechanism Profile
(Actin-binding peptide; cytoskeletal regulator; angiogenesis modulator – research use only)
TB-500 is a synthetic fragment of Thymosin β4, a highly conserved 43-amino-acid peptide involved in G-actin binding, F-actin polymerization, endothelial migration, and angiogenic signaling.
In vitro, TB-500 influences cytoskeletal organization, extracellular matrix (ECM) remodeling, and transcription of angiogenesis-related genes through PI3K/Akt, MAPK/ERK, and NO/eNOS pathways.
✅ 1. Primary Molecular Target
G-actin (Globular Actin)
TB-500 binds monomeric G-actin, regulating:
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Actin polymerization → F-actin fiber formation
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Lamellipodia generation
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Directional cell migration
Actin remodeling affects focal adhesion proteins, integrins, and ECM-interaction signaling.
✅ 2. Core Signaling Pathways
A. PI3K → Akt Pathway
Activation of PI3K leads to:
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Akt phosphorylation
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Increased cell survival, motility, and angiogenic transcription
Common downstream genes:
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BCL2, BCL-XL (anti-apoptotic)
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HIF-1α (oxygen-response regulator)
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VEGFA
B. MAPK / ERK Pathway
TB-500 stimulates:
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Ras → Raf → MEK → ERK1/2 phosphorylation
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ERK translocates to nucleus → transcription of immediate-early genes
ERK-responsive genes:
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FOS, JUN, EGR1
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MMP2, MMP9 (matrix remodeling)
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COL1A1, FN1 (Fibronectin)
C. eNOS / Nitric Oxide (NO) Axis
Akt and ERK signaling can elevate:
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eNOS phosphorylation (NOS3)
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Nitric oxide production
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Vasodilation & endothelial migration in vascular culture models
✅ 3. Cytoskeletal Regulation
TB-500 influences proteins that shape actin architecture:
| Protein / Gene | Role |
|---|---|
| ACTB / ACTG1 (β- and γ-actin) | Actin monomers for polymerization |
| Profilin (PFN1) | Accelerates actin filament elongation |
| Cofilin (CFL1) | Actin turnover / depolymerization |
| Arp2/3 Complex | Branching of actin fibers |
| VASP | Focal adhesion and membrane protrusion |
✅ 4. ECM Remodeling & Angiogenic Regulation
TB-500 modulates extracellular matrix enzymes and growth factors:
| Target | Effect |
|---|---|
| MMP2 & MMP9 | Basement membrane degradation, migration pathways |
| COL1A1, COL3A1 | Collagen expression in structural models |
| FGF-2, VEGFA | Angiogenic signaling |
| TGF-β1 | ECM deposition and fibroblast activity |
✅ 5. Representative Gene Targets
| Functional Class | Genes Commonly Monitored |
|---|---|
| Cytoskeleton | ACTB, ACTG1, PFN1, CFL1, ARPC2 |
| Angiogenesis | VEGFA, KDR/VEGFR2, FGF2, HIF-1α |
| ECM Remodeling | MMP2, MMP9, COL1A1, FN1 |
| Survival Signaling | BCL2, BCL-XL, mTOR |
| Immediate-Early Response | FOS, JUN, EGR1 |
✅ 6. Second Messengers
| Messenger | Mechanistic Role |
|---|---|
| NO (Nitric Oxide) | Vasodilation, endothelial migration |
| Ca²⁺ | Cytoskeletal contraction & focal adhesion turnover |
| ERK1/2 | Mitogenic gene transcription |
| Akt | Cell survival & angiogenic gene activation |
✅ Mechanistic Summary
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Actin-binding peptide regulating G-actin → F-actin polymerization
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Activates PI3K/Akt, MAPK/ERK, and eNOS pathways
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Drives transcription of angiogenesis, ECM remodeling, cytoskeletal, and cell survival genes
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Affects MMP2/9, VEGF, collagen, and integrin-linked motility machinery in research systems
Research-Only Classification
Thymosin Beta-4 (TB-500) is supplied exclusively for controlled in-vitro laboratory research.
Not approved for human or animal administration, therapeutic use, or any biological application outside research environments.