Yamada E, Mizutani H, Yoshida T, Isoda K, Shimizu M
Department of Dermatology, Faculty of Medicine, Mie University, Tsu, Japan.
J Dermatol Sci. 1999 Dec;22(1):45-53. doi: 10.1016/s0923-1811(99)00047-x.
Retinoids are strong tissue modifiers and have been used to treat severe acne, keloids and photo-aged skin. Tocoretinate (TR), ester bound retinoic acid and tocopherol, has been topically applied for skin ulcers and, more recently, for sclerotic skin diseases. To clarify the mechanism of tissue softening by retinoids and TR, we investigated their effects on the contraction of hydrated type-1 collagen gel matrices by human dermal fibroblasts and on tenascin-C expression. TR, 13-cis-retinoic acid/isotretinoin and all trans-retinoic acid significantly inhibited collagen gel matrices contraction at concentrations from 10(-4) to 10(-8) M without significant changes of the fibroblast growth. TR and the other two retinoids dose-dependently induced tenascin-C expression in the fibroblasts. Since tenascin-C is involved in cellular detachment and tissue remodeling, these results suggest that TR and other retinoids down-regulated the tensile tension of fibroblasts in collagen gel matrices by the induction of tenascin-C.
维甲酸是强效的组织调节剂,已被用于治疗重度痤疮、瘢痕疙瘩和光老化皮肤。托可维甲酸(TR),即与视黄酸结合的酯和生育酚,已被局部应用于皮肤溃疡,最近也用于治疗硬化性皮肤病。为了阐明维甲酸和TR使组织软化的机制,我们研究了它们对人真皮成纤维细胞收缩水合I型胶原凝胶基质的影响以及对肌腱蛋白-C表达的影响。TR、13-顺式维甲酸/异维甲酸和全反式维甲酸在浓度为10^(-4)至10^(-8) M时显著抑制胶原凝胶基质收缩,而成纤维细胞生长无明显变化。TR和其他两种维甲酸剂量依赖性地诱导成纤维细胞中肌腱蛋白-C的表达。由于肌腱蛋白-C参与细胞脱离和组织重塑,这些结果表明TR和其他维甲酸通过诱导肌腱蛋白-C下调了成纤维细胞在胶原凝胶基质中的拉伸张力。