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吡美莫司可增加黑素细胞的黑素生成和迁移。

Pimecrolimus increases the melanogenesis and migration of melanocytes .

作者信息

Xu Ping, Chen Jie, Tan Cheng, Lai Ren-Sheng, Min Zhong-Sheng

机构信息

First Clinical College, Nanjing University of Chinese Medicine, Nanjing 210029, China.

Department of Dermatology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China.

出版信息

Korean J Physiol Pharmacol. 2017 May;21(3):287-292. doi: 10.4196/kjpp.2017.21.3.287. Epub 2017 Apr 21.

Abstract

Vitiligo is an intriguing depigmentary disorder and is notoriously difficult to be treated. The ultimate goal of vitiligo treatment is to replenish the lost melanocytes by immigration from hair follicle and to restore the normal function of melanogenesis by residual melanocytes. There are two types of topical calcineurin inhibitors called tacrolimus and pimecrolimus, and are recommended as the first-line treatments in vitiligo. Although pimecrolimus is efficacious for the repigmentation of vitiligo, its intrinsic mechanisms have never been investigated in vitro. This research aimed to study the ability of pimecrolimus on stimulating melanogenesis, melanocyte migration and MITF (microphthalmia associated transcription factor) protein expression. Results showed that pimecrolimus at the dosages of 1, 10, 10 nM were neither mitogenic nor cytotoxic to melanocytes. The addition of pimecrolimus at 10, 10 and 10 nM significantly increased intracellular tyrosinase activity, which was consistent with the elevated content of melanin content at the same concentrations. The peak effect was seen at 72 h in response to 10 nM pimecrolimus. Results of the wound scratch assay and Transwell assays indicate that pimecrolimus is effective in facilitating melanocyte migration on a collagen IV-coated surface. In addition, MITF protein yield reached the highest by pimecrolimus at 10 nM. In brief, pimecrolimus enhances melanin synthesis as well as promotes migration of melanocytes directly, possibly via their effects on MITF protein expression.

摘要

白癜风是一种引人关注的色素脱失性疾病,治疗难度极大。白癜风治疗的最终目标是通过毛囊中黑素细胞的迁移来补充缺失的黑素细胞,并通过残余的黑素细胞恢复黑素生成的正常功能。有两种外用钙调神经磷酸酶抑制剂,即他克莫司和吡美莫司,被推荐作为白癜风的一线治疗药物。尽管吡美莫司对白癜风的色素再生有效,但其内在机制从未在体外进行过研究。本研究旨在探讨吡美莫司刺激黑素生成、黑素细胞迁移及小眼相关转录因子(MITF)蛋白表达的能力。结果显示,1、10、100 nM剂量的吡美莫司对黑素细胞既无促有丝分裂作用也无细胞毒性作用。添加10、100和1000 nM的吡美莫司可显著提高细胞内酪氨酸酶活性,这与相同浓度下黑色素含量的升高相一致。在100 nM吡美莫司作用72小时时观察到峰值效应。伤口划痕试验和Transwell试验结果表明,吡美莫司在IV型胶原包被的表面上能有效促进黑素细胞迁移。此外,100 nM的吡美莫司使MITF蛋白产量达到最高。简而言之,吡美莫司可能通过影响MITF蛋白表达直接增强黑色素合成并促进黑素细胞迁移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ed9/5409113/fc3892ed7fbf/kjpp-21-287-g001.jpg

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