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In vivo and in vitro evidence of dermal fibroblasts influence on human epidermal pigmentation

机译:真皮成纤维细胞对人表皮色素沉着影响的体内和体外证据

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Using chimeric human epidermal reconstructs, we previously demonstrated that epidermal pigmentation is dependent upon the phototype of melanocytes. We report here several lines of experimental evidence for dermal modulation of human epidermal pigmentation. First, phototype II-III epidermal reconstructs grafted on the back of immunotolerant Swiss nuu mice developed a patchy pigmentation dependent on the presence of colonizing human or mouse fibroblasts. Similarly, human white Caucasoid split-thickness skin xenografted on the same mouse strain became black within 3 months and histochemistry revealed a phototype VI pattern of melanin distribution. In vitro, human fibroblasts colonizing human dead de-epidermized dermis (DDD) induced a decrease in epidermal pigmentation whereas mouse (Swiss nuu) fibroblasts increased epidermal pigmentation. Conditioned medium from mice (Swiss nuu) fibroblasts also increased pigmentation whereas conditioned medium from human fibroblasts had no significant effect. Lastly, epidermal reconstructs made with normal or vitiligo keratinocytes and/or normal or vitiligo melanocytes from the same donor grown on DDD originating from several donors of the same clinical phototype did not pigment similarly and no specific dermal influence was noted for vitiligo. Thus, fibroblast secretion and acellular dermal connective tissue itself significantly influence melanocyte proliferation and melanin distribution/degradation. Our study suggests that murine fibroblasts are more potent than human fibroblasts in secreting soluble factors which can act directly on pigmentation, such as SCF, or activate keratinocytes to produce basement membrane proteins or melanogenic factors.
机译:使用嵌合的人类表皮重建物,我们以前证明了表皮色素沉着取决于黑素细胞的光型。我们在这里报告了人类表皮色素沉着的皮肤调节的几行实验证据。首先,在免疫耐受的瑞士nu / nu小鼠的背部移植了光敏的II-III型表皮重建物,其斑驳的色素沉着取决于定植的人类或小鼠成纤维细胞的存在。同样,异种移植到同一小鼠品系上的人类白高加索人劈开厚度皮肤在3个月内变黑,组织化学显示黑色素分布的光型VI模式。在体外,定植于人死去表皮真皮(DDD)的人成纤维细胞诱导表皮色素沉着减少,而小鼠(Swiss nu / nu)成纤维细胞增加表皮色素沉着。来自小鼠(Swiss nu / nu)成纤维细胞的条件培养基也增加了色素沉着,而来自人成纤维细胞的条件培养基没有明显的作用。最后,由正常或白癜风的角质形成细胞和/或正常或白癜风的黑素细胞来自同一临床光型的多个供体的DDD上生长的同一供体的正常或白癜风黑素细胞,其表皮重建物没有类似的色素沉着,并且未发现对白癜风有特殊的皮肤影响。因此,成纤维细胞分泌和无细胞真皮结缔组织本身显着影响黑素细胞增殖和黑素分布/降解。我们的研究表明,鼠类成纤维细胞在分泌可直接作用于色素沉着的可溶性因子(例如SCF)或激活角质形成细胞以产生基底膜蛋白或黑色素生成因子方面,比人成纤维细胞更有效。

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