Skin and hair follicle fibroblasts differentially express POMC peptides, receptors and associated processing convertases during the hair growth cycle and in vitro– implications for fibroblast topographic differentiation in skin

Abstract

Mesenchymal cells are involved in reciprocal mesenchymal–epithelial interactions during development and growth of skin and its appendages. Fibroblasts exhibit topographic differentiation and so constitute a highly diverse family of cells with distinct and characteristic traits. This heterogeneity is also seen in the skin where hair growth inductive fibroblasts called follicular papilla (FP) fibroblasts are distinct from fibroblasts of the connective tissue sheath (CTS), and both, in turn, are distinct from peripheral interfollicular dermal fibroblasts (DFs). POMC peptides and their cognate receptors are expressed variably by several skin cells types, including fibroblasts. However, it is not clear how the POMC system is regulated in different skin fibroblasts populations. We characterized the expression of the POMC peptide family and their receptors and pro‐hormone convertases (PCs) in human haired scalp during the hair growth cycle and in matched sets of DF, FP and CTS fibroblasts cultured from normal adult male scalp. Expression of POMC peptides, PC 2 and µ‐OR in FP fibroblasts was highest during anagen. By contrast, β‐end, 7B2 and PC1 were broadly undetectable during anagen but expression levels increased considerably during the apoptosis‐driven catagen phase. Matched sets of cultured FP and DF fibroblasts showed similar protein expression levels of α‐MSH, ACTH, PC2, 7B2, µ‐OR and MC1‐R. However, FP cells expressed higher levels of PC1 and β‐end peptide and higher µ‐OR mRNA levels than DF cells. Thus, follicular and interfollicular fibroblasts represent heterogeneous subpopulations that are likely to respond variably to POMC peptides.