BASAL MEMBRANE HEPARAN-SULFATE PROTEOGLYCAN EXPRESSION DURING WOUND-HEALING IN HUMAN SKIN

Heparan sulphate proteoglycans (HSPGs) are integral components of the basement membrane (BM) in various tissues, HSPGs are important in the assembly and structure of the BM, and their putative functions include regulation of basement membrane permeability binding of growth factor s, and a role in cellular adhesion, In this study the expression of HS PG was examined during wound healing in human skin, using monoclonal a ntibodies (MAbs) that recognize the HSPG core protein and two differen t heparan sulphate (HS) epitopes, and the dynamics of HSPG expression were investigated in relation to epidermal cellular proliferation and permeability of the BM. Healing of excisional mounds in healthy volunt eers was studied from day 0 up to 1 year. Intact human skin showed str ong continuous staining of the dermo-epidermal BM and the vascular BM with all MAbs. Up to dag 4 after wounding, staining for HSPG was absen t under the ingrowing epidermis, with any of the MAbs, indicating that no complete BM was present. From day 7 onwards, the EM of the neo-epi dermis showed positive staining for the HSPG core protein and a low su lphated HS epitope, and after day 14, the staining intensity was simil ar to normal skin. The staining patterns of these HSPG epitopes were s imilar to that of laminin, The staining pattern with a MAb against an epitope in the highly sulphated part of HS was found to be distinct fr om the other BM markers studied, This epitope was absent under the neo -epidermis up to 2 months after wounding. One pear after wounding, the epitope was found to be present again. We observed that only in the t ime period between 2 months and 1 year had the epidermis normalized wi th respect to the number of cycling cells and the absence of high mole cular weight plasma proteins. These findings suggest a correlation bet ween normalization of epidermal proliferation, BM permeability, and re generation of BM HS. It is proposed that complete RM maturation follow ing skin mounding is a slow process and mag account for the epidermal abnormalities that persist for a considerable period of time after wou nd healing. (C) 1997 John Wiley & Sons, Ltd.