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外源性添加 C-木吡喃糖苷衍生物可刺激角质形成细胞硫酸皮肤素合成并促进迁移。

Exogenous addition of a C-xylopyranoside derivative stimulates keratinocyte dermatan sulfate synthesis and promotes migration.

机构信息

Division of Dermatology, University of California, San Diego and Veterans Affairs San Diego Health Care System, San Diego, California, United States of America.

出版信息

PLoS One. 2011;6(10):e25480. doi: 10.1371/journal.pone.0025480. Epub 2011 Oct 5.

Abstract

As C-Xyloside has been suggested to be an initiator of glycosaminoglycan (GAG) synthesis, and GAGs such as Dermatan sulfate (DS) are potent enhancers of fibroblast growth factor (FGF)--10 action, we investigated if a C-Xylopyranoside derivative, (C-β-D-xylopyranoside-2-hydroxy-propane, C-Xyloside), could promote DS production by cultured normal human keratinocytes, how this occurs and if C-Xyloside could also stimulate FGF-dependent cell migration and proliferation. C-Xyloside-treated keratinocytes greatly increased secretion of total sulfated GAGs. Majority of the induced GAG was chondroitin sulfate/dermatan sulfate (CS/DS) of which the major secreted GAG was DS. Cells lacking xylosyltransferase enzymatic activity demonstrated that C-Xyloside was able to stimulate GAG synthesis without addition to core proteins. Consistent with the observed increase in DS, keratinocytes treated with C-Xyloside showed enhanced migration in response to FGF-10 and secreted into their culture media GAGs that promoted FGF-10-dependent cellular proliferation. These results indicate that C-Xyloside may enhance epithelial repair by serving as an initiator of DS synthesis.

摘要

由于 C-木糖苷已被认为是糖胺聚糖 (GAG) 合成的启动子,而硫酸皮肤素 (DS) 等 GAG 是成纤维细胞生长因子 (FGF)-10 作用的有效增强剂,我们研究了 C-木糖苷衍生物(C-β-D-木糖苷-2-羟丙烷,C-木糖苷)是否可以促进培养的正常人角质形成细胞产生 DS,这种情况是如何发生的,以及 C-木糖苷是否也可以刺激 FGF 依赖性细胞迁移和增殖。C-木糖苷处理的角质形成细胞大大增加了总硫酸化 GAG 的分泌。诱导的 GAG 主要是软骨素硫酸盐/硫酸皮肤素 (CS/DS),其中主要分泌的 GAG 是 DS。缺乏木糖基转移酶酶活性的细胞表明,C-木糖苷能够刺激 GAG 合成,而无需添加核心蛋白。与观察到的 DS 增加一致,用 C-木糖苷处理的角质形成细胞显示出对 FGF-10 的迁移增强反应,并分泌到其培养基中的 GAG 促进 FGF-10 依赖性细胞增殖。这些结果表明,C-木糖苷可能通过作为 DS 合成的启动子来增强上皮修复。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf17/3187761/aaf6d1e49165/pone.0025480.g001.jpg

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