title: Cyclic stretch induces upregulation of endothelin-1 with keratinocytes in vitro: possible role in mechanical stress-induced hyperpigmentation.
abstract: The aim of this study was to investigate the possible pathological relation between mechanical stress and hyperpigmentation. We did this by investigating the influence of cyclic stretch on the expression of keratinocyte- and fibroblast-derived melanogenetic paracrine cytokines in vitro. Using primary human keratinocytes and fibroblasts, alterations of mRNA expression of melanogenetic paracrine cytokines due to cyclic stretch were investigated using a real-time polymerase chain reaction (PCR). The cytokines included basic fibroblast growth factor (bFGF), stem cell factor (SCF), granulocyte/macrophage colony-stimulating factor, interleukin-1α, and endothelin-1 (ET-1) for keratinocytes and bFGF, SCF, and hepatocyte growth factor for fibroblasts. The dose dependence of keratinocyte-derived ET-1 upregulation was further investigated using real-time PCR and an enzyme-linked immunosorbent assay. We also investigated the effects of cyclic stretch on the proliferation and differentiation of keratinocytes. Among the melanogenetic paracrine cytokines investigated, keratinocyte-derived ET-1 was consistently upregulated in all four cell lines. The degree of upregulation increased with the degree of the length and frequency of the stretch; in contrast, cell number and differentiation markers showed no obvious alterations with cyclic stretch. Keratinocyte-derived ET-1 upregulation possibly plays a significant role in the pathogenesis of pigmented disorders, such as friction melanosis, caused by mechanical stress.
authors.affiliation: Department of Plastic Surgery, Kyorin University School of Medicine, Shinkawa, Mitaka-shi, Tokyo, Japan. masakazukurita@gmail.com
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kurita
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Okazaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujino
authors.forename: Akihiko
authors.initials: A
authors.lastname: Takushima
authors.forename: Kiyonori
authors.initials: K
authors.lastname: Harii
mesh_terms: D002478:Cells, Cultured; D019332:Endothelin-1 / Q000096:biosynthesis*; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D006801:Humans; D017495:Hyperpigmentation / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D008548:Melanosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D013314:Stress, Mechanical; D015854:Up-Regulation
chemical_list: D019332:Endothelin-1