Re: Hypothesis of the Pathology and Healing Process of E.C.

I have posted below some pretty good information on the process of re-epithelialization, the process whereby the keratinocytes migrate all the way to the other side of the open wound to cover the wound. Re-epithelialization is classified as part of the proliferative phase of wound healing, which follows the inflammatory phase. Two important points should be taken from the text below:

1)The keratinocytes (white stuff on our lips) will always continue to proliferate only until they come in contact with the opposing keratinocytes. "Once contact is established with opposing keratinocytes, mitosis and migration stop, and in the skin, the cells differentiate into a stratified squamous epithelium above a newly generated basement membrane."

2)Re-epithilialization is important to contract the wound. "Re-epithelialization is critical to optimal wound healing not only because of reformation of a cutaneous barrier, but because of its role in wound contraction."

Thus we will be in a state of CHRONIC INFLAMMATION SECONDARY TO ABBERANT RE-EPITHELIAZATION. It seems that if we allow re-epithelialization to occur (I mean 100% to the fullest) we might be able to heal the lips.


Source:
http://www.rndsystems.com/mini_review_detail_objectname_MR02_CytokineWoundHea...

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Re-epithelialization

Clearance of debris, foreign agents, and/or infectious organisms promotes resolution of inflammation, apoptosis, and the ensuing repair response that encompasses overlapping events involved in granulation tissue, angiogenesis, and re-epithelialization. Within hours, epithelial cells begin to proliferate, migrate and cover the exposed area to restore the functional integrity of the tissue. Re-epithelialization is critical to optimal wound healing not only because of reformation of a cutaneous barrier, but because of its role in wound contraction. Immature keratinocytes produce matrix metalloproteases (MMPs) and plasmin to dissociate from the basement membrane and facilitate their migration across the open wound bed in response to chemoattractants. The migration of epithelial cells occurs independently of proliferation, and depends upon a number of possible processes including growth factors, loss of contact with adjacent cells, and guidance by active contact. TGF-β1 stimulates migration of keratinocytes in vitro,6,19 possibly by integrin regulation and/or provisional matrix deposition.20 Behind the motile epidermal cells, basal cell keratinocyte proliferation is mediated by the local release of growth factors, with a parallel up-regulation of growth factor receptors including TNF-α, heparin-binding epidermal growth factor (EGF) and keratinocyte growth factor (KGF or FGF-7).21-23 Such growth factors are released not only by keratinocytes themselves, acting in an autocrine fashion, but also by mesenchymal cells and macrophages (Table 1), as paracrine mediators.24,25 Numerous animal models in which cytokine genes have been deleted or over-expressed have provided further evidence that such factors are involved in the process of epithelialization.23 TGF-β1, and -β2 are potent inhibitors of keratinocyte proliferation, with the Smad3 pathway implicated as the negative modulator.6 Since epithelialization is significantly accelerated in mice null for the Smad3 gene, with unchecked keratinocyte proliferation, but impaired migration in response to TGF-β1, the implication is that the early proliferative event is critical to normal epithelialization.6 Once contact is established with opposing keratinocytes, mitosis and migration stop, and in the skin, the cells differentiate into a stratified squamous epithelium above a newly generated basement membrane. Other factors secreted by keratinocytes may exert paracrine effects on dermal fibroblasts and macrophages. One such factor is a keratinocyte-derived non-glycosylated protein termed secretory leukocyte protease inhibitor (SLPI), which inhibits elastase, mast cell chymase, NF-?B and TGF-β1 activation. In rodents, SLPI is a macrophage-derived cytokine with autocrine and paracrine activities,26, 27 but production by human macrophages has not yet been demonstrated. In mice, an absence of this mediator of innate host defense (SLPI null) is associated with aberrant healing.26 Tweet