What growth factor is keloid formation associated with?

Keloid Formation is Associated with Increased Transforming Growth Factor

Keloid formation is most strongly associated with an increased amount of transforming growth factor (TGF-β), particularly the TGF-β3 isoform 1, 2. This growth factor plays a central role in the pathogenesis of keloids through its effects on fibroblast proliferation, collagen production, and extracellular matrix deposition.

Evidence Supporting TGF-β in Keloid Formation

Molecular Mechanisms

• TGF-β is a key mediator in wound healing that promotes:

  • Increased extracellular matrix production
  • Decreased collagenase production
  • Fibroblast differentiation into myofibroblasts 1
  • Enhanced collagen deposition 1

• In keloid tissue specifically:

  • TGF-β3 expression is significantly elevated (5-fold higher) compared to normal skin 1
  • TGF-β shows diffuse epidermal expression (90% of keloid samples) compared to limited basal layer expression in normal skin (20%) 3
  • TGF-β expression is particularly pronounced in early/immature keloid scars 3

Cellular Response Differences

• Normal fibroblasts show growth inhibition when exposed to TGF-β
• Keloid fibroblasts show resistance to this inhibitory effect 1
• Keloid fibroblasts demonstrate higher per-cell TGF-β1 production compared to fetal fibroblasts (which exhibit scar-free healing) 4

Other Growth Factors in Keloid Formation

While TGF-β is the primary growth factor associated with keloid formation, other growth factors play supporting roles:

• Platelet-derived growth factor (PDGF): Involved in wound healing and stimulates fibroblast proliferation, but not as strongly implicated in keloid pathogenesis as TGF-β 1

• Epidermal growth factor (EGF): Promotes epithelial cell proliferation during wound healing but has not been specifically identified as a major driver of keloid formation 1

• Tumor necrosis factor (TNF): While involved in inflammatory responses, it has not been demonstrated to have the same level of association with keloid formation as TGF-β 1, 2

Clinical Implications

The identification of TGF-β as a key mediator in keloid formation has important therapeutic implications:

• Targeting TGF-β may be most beneficial in early keloid formation 3
• Therapeutic approaches should consider targeting both dermal fibroblasts and keratinocytes, as epidermal TGF-β expression is significantly elevated in keloids 3
• Agents that block TGF-β activity, such as tamoxifen, have shown promise in decreasing TGF-β1 production by keloid fibroblasts 4

Important Caveats

• Despite the strong association between TGF-β and keloid formation, studies have not found significant differences in plasma TGF-β1 levels between keloid patients and controls 5
• Common polymorphisms in TGF-β receptors have not been associated with keloid susceptibility, suggesting that local tissue factors rather than genetic receptor variations may be more important 6
• The relationship between TGF-β and keloid formation appears to be most significant in early/developing keloids rather than established lesions 3

Therefore, based on the available evidence, the answer is A. Transforming growth factor.