Abstract
The epidermal basement membrane deteriorates with aging. We previously reported that basement membrane reconstruction not only serves to maintain epidermal stem/progenitor cells in the epidermis, but also increases collagen fibrils in the papillary dermis. Here, we investigated the mechanism of the latter action. Collagen fibrils in the papillary dermis were increased in organotypic human skin culture treated with matrix metalloproteinase and heparinase inhibitors. The expression levels of COL5A1 and COL1A1 genes (encoding collagen type V α 1 chain and collagen type I α 1 chain, respectively) were increased in fibroblasts cultured with conditioned medium from a skin equivalent model cultured with the inhibitors and in keratinocytes cultured on laminin-511 E8 fragment-coated plates. We then examined cytokine expression, and found that the inhibitors increased the expression of PDGF-BB (platelet-derived growth factor consisting of two B subunits) in epidermis. Expression of COL5A1 and COL1A1 genes was increased in cultured fibroblasts stimulated with PDGF-BB. Further, the bifunctional inhibitor hydroxyethyl imidazolidinone (HEI) increased skin elasticity and the thickness of the papillary dermis in the skin equivalent. Taken together, our data suggests that reconstructing the basement membrane promotes secretion of PDGF-BB by epidermal keratinocytes, leading to increased collagen expression at the papillary dermis.
Highlights
The epidermal basement membrane deteriorates with aging
Since the decrease of basement membrane component laminin-511 observed histologically was matched by a reduction of the gene expression with aging[10], we measured the expression levels of the COL1A1, COL3A1 and COL5A1 genes in cultured human fibroblasts from donors of different ages
We previously reported that the basement membrane was damaged as a result of activation of MMPs and heparinase in the epidermis after UV irradiation[6,7], and treatment of organotypic human skin and skin equivalent models with both MMP and heparinase inhibitors promoted the formation of basement membrane at the dermal–epidermal junction and resulted in the appearance of thicker collagen fibrils in the papillary d ermis[11]
Summary
The epidermal basement membrane deteriorates with aging. We previously reported that basement membrane reconstruction serves to maintain epidermal stem/progenitor cells in the epidermis, and increases collagen fibrils in the papillary dermis. Collagen fibrils in the papillary dermis were increased in organotypic human skin culture treated with matrix metalloproteinase and heparinase inhibitors. Our data suggests that reconstructing the basement membrane promotes secretion of PDGF-BB by epidermal keratinocytes, leading to increased collagen expression at the papillary dermis. Abbreviations MMP(s) Matrix metalloproteinase(s) DEJ Dermal–epidermal junction BM Basement membrane SE Skin equivalent OC Organotypic culture PDGF Platelet-derived growth factor PDGFR-β Platelet-derived growth factor receptor-beta. The epidermal basement membrane (BM) at the dermal–epidermal junction is a ubiquitous sheet-like structure that binds the dermis and the epidermis of the skin together. It is mainly composed of type IV and type VII collagens, laminin-511, laminin-332, nidogen, and perlecan[5]. The corresponding gene expression levels in fibroblasts are reduced[9]
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