P5.52 FOLLICULAR AND INTERFOLLICULAR FIBROBLASTS DIFFERENTIALLY EXPRESS PRO-OPIOMELANOCORTIN PEPTIDES, RECEPTORS & PROCESSING CONVERTASES IN VITRO AND DURING THE HAIR GROWTH CYCLE - IMPLICATIONS FOR FIBROBLAST TOPOGRAPHIC DIFFERENTIATION IN SKIN.

S Kauser, ROS Karoo, M Böhm¹, DJ Tobin

Dept. of Biomedical Sciences, University of Bradford, England & ¹Dept. of Dermatology, University of Münster, Münster , Germany

Mesenchymal cells are involved in reciprocal mesenchymal-epithelial interactions critical for development and growth of skin and its appendages. Fibroblasts exhibit significant topographic differentiation and so constitute a highly diverse family of cells with distinct and characteristic traits. Fibroblast phenotypic heterogeneity is also seen in the skin, where hair growth-inductive fibroblasts called follicular dermal papilla (DP) fibroblasts are distinct from fibroblasts of the connective tissue/dermal sheath (DS). Both follicular fibroblast subtypes are, in turn, distinct from neighboring interfollicular dermal fibroblasts (DF). POMC peptides and their cognate receptors are expressed by several skin cells types, and recent evidence suggest that the POMC system is active also in fibroblasts. a-MSH may protect fibroblasts against UVB-induced apoptosis, and POMC peptides cleavage in fibroblasts can be modulated by the extracellular matrix relevant cytokines TNF-a and TGF-b. However, it is not clear how the POMC system is regulated in different skin fibroblasts populations.

Thus, we characterised immunohisto(cyto)chemically the expression of the POMC peptide family, their receptors, and associated pro-hormone convertases (PC) in human haired scalp during the hair growth cycle and in matched sets of DF, DP and DS fibroblasts cultured from normal adult male scalp.

Expression of POMC peptides, PC 2 and m-OR in DP fibroblasts was highest during anagen. By contrast, b-end, 7B2 and PC1 were broadly undetectable during anagen but expression levels increased considerably during the apoptosis-driven catagen phase. Matched sets of cultured DP and DF fibroblasts showed similar protein expression levels of a-MSH, ACTH, PC2, 7B2, m-OR and MC1-R. However, DP cells expressed higher levels of PC1 and b-end peptide and higher m-OR mRNA levels than DF cells. Thus, follicular and interfollicular fibroblasts represent heterogeneous sub-populations that are likely to respond variably to POMC peptides. These differences are likely to reflect the striking variations in the status of these fibroblasts subtypes during hair growth and cycling compared to the relatively steady-state conditions of non-injured dermis.