Keloids: a faulty switch in wound healing?

Keloids emerge when normal wound healing is disturbed. Although much is known about the pathogenesis, the reasons for induction of keloids still remain unclear.

“Normal wound healing is like a good story: there is a beginning, a middle, and an end,” Prof. Greg Goodman (Monash University, Australia) began his lecture [1]. Normal wound healing starts with an inflammatory phase (see Figure), with activation of the clotting cascade as well as action of cytokines and the attraction of immune cells. Next is the proliferative phase, which lasts for about 6-7 weeks. The fibrin plug is replaced by granulation tissue, fibroblasts generate collagen 3, extracellular matrix and re-epithelialisation takes place as keratinocytes migrate across the wound surface. Angiogenesis also induces the production of immature leaky blood vessels to allow easy access of nutrients. During the final remodelling phase, the granulation tissue changes from type 3 collagen to type 1, the immature vessels regress, and the now stronger scar tissue contracts.

Figure: The 3 phases of normal wound healing. Modified from [1]



“We need to think of keloids as a faulty switch in the transition from the proliferation to the remodelling phase with a failure of apoptotic control of reticular dermal healing,” explained Prof. Goodman. Overexpressed growth factors and increased activity by fibroblasts can be observed in keloids; proinflammatory factors continue to be upregulated; and a gap between extracellular matrix stiffness and cellular stiffness increases the likelihood of keloid progression [2]. Lastly, keloids have a 20-fold increase of collagen levels, the fibroblasts proliferate faster and the balance is lost between pro- and anti-inflammatory mediators [1]. There may be a genetic basis for the inability to turn of the proliferative phase and enter the remodelling phase. “We have a few details of what is abnormal and how it happens, but virtually no knowledge of why it happens,” concluded Prof. Goodman.

1. 
   
   1. Goodman G. 24th World Congress of Dermatology, 10-15 June 2019, Milan, Italy.
   2. Huang C et al. Int Wound J. 2017;14: 764-771.

 



Posted on 26 August, 201921 March, 2021