Regeneration of collagen fibrils at the papillary dermis by reconstructing basement membrane at the dermal–epidermal junction

DOI DOI PubMed オープンアクセス

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<jats:title>Abstract</jats:title><jats:p>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 <jats:italic>COL5A1</jats:italic> and <jats:italic>COL1A1</jats:italic> 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 <jats:italic>COL5A1</jats:italic> and <jats:italic>COL1A1</jats:italic> 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.</jats:p>

収録刊行物

  • Scientific Reports

    Scientific Reports 12 2021-07-26

    Springer Science and Business Media LLC

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