| First Author | Thomason HA | Year | 2012 |
| Journal | J Pathol | Volume | 227 |
| Issue | 3 | Pages | 346-56 |
| PubMed ID | 22407785 | Mgi Jnum | J:185465 |
| Mgi Id | MGI:5428816 | Doi | 10.1002/path.4016 |
| Citation | Thomason HA, et al. (2012) Direct evidence that PKCalpha positively regulates wound re-epithelialization: correlation with changes in desmosomal adhesiveness. J Pathol 227(3):346-56 |
| abstractText | Non-healing wounds cause considerable patient morbidity and represent a significant economic burden. Central to wound repair is re-epithelialization, a crucial process involving the modulation of cell adhesion to allow keratinocyte migration to cover the exposed underlying tissues. The cellular mechanisms regulating the earliest stages of re-epithelialization are unclear. We present the first direct evidence that protein kinase Calpha (PKCalpha) plays an important role in regulating wound re-epithelialization. In PKCalpha(-/-) mice re-epithelialization is delayed, while in novel bitransgenic mice over-expressing constitutively active PKCalpha it is accelerated. These effects are not due to changes in keratinocyte proliferation, apoptosis or intrinsic cell motility. Instead, they correlate with changes in desmosomal adhesiveness, delay being preceded by retained desmosomal hyper-adhesiveness and acceleration with a rapid switch to desmosomal Ca(2+) -dependence. We demonstrate mechanistic conservation in acute human wounds where PKCalpha localizes to wound edge desmosomes, which become Ca(2+) -dependent. However, in chronic wounds PKCalpha remains cytoplasmic and desmosomes fail to switch from the hyper-adhesive state. These results throw new mechanistic light on the earliest stages of wound re-epithelialization and suggest activation of PKCalpha as a new therapeutic strategy for non-healing wounds. Copyright (c) 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
