In psoriasis the non-lesional skin shows alterations at the dermo-epidermal junction (DEJ) compared to healthy skin. Among these alterations we previously found COMP protein overexpression in psoriatic non-lesional skin. Because there was no information about a functional role of this protein in the epidermis, we studied its effect on keratinocytes. Healthy, non-lesional and lesional psoriatic skin tissues were used for immunofluorescence staining (COMP, β1-integrin), for western blot (COMP) and cultured fibroblasts for COMP mRNA expression analysis. To elucidate the effect of COMP on cell proliferation bromodeoxyuridine/5-bromo-2'-deoxyuridine assay and antibody-blocking-based experiments of α5-integrin and β1-integrin were applied using cell culture and ex vivo wound healing models. We found that COMP levels in the papillary dermis were higher in non-lesional skin than in healthy skin due to increased expression by fibroblasts. COMP partially co-localized with β1-integrin on basal keratinocytes, and this co-localization was most prominent in non-lesional skin. In lesions, COMP deposition was partially discontinuous at the DEJ. In in vitro cultures COMP reduced keratin 17 (K17), an indicator of keratinocyte activation and it inhibited keratinocyte proliferation via α5β1-integrin. It is well known that in non-lesional psoriatic skin there is no keratinocyte hyperproliferation and K17 expression, in spite of increased α5β1 integrin expression. Our results suggest that COMP elevation at the DEJ region in non-lesional skin could be responsible for inhibiting epidermal hyperproliferation. The antiproliferative effect of COMP is likely to be relevant to other skin diseases in which chronic non-healing wounds are coupled with massive COMP accumulation.

Cartilage oligomeric matrix protein (COMP) negatively influences keratinocyte proliferation via α5β1-integrin: Potential relevance of altered COMP expression in psoriasis