Two dicarbonyl compounds, 3-deoxyglucosone and methylglyoxal, differentially modulate dermal fibroblasts
Two dicarbonyl compounds, 3-deoxyglucosone and methylglyoxal, differentially modulate dermal fibroblasts
复制标题
DOI：
10.1016/j.matbio.2009.09.007
复制
发表时间：
2010-03-01
期刊：
影响因子：
6.9
通讯作者：
Artlett, Carol M.
中科院分区：
文献类型：
--
作者：
Sassi-Gaha, Sihem;Loughlin, Danielle T.;Artlett, Carol M.
晚期糖基化终产物随着饮食和年龄的变化在长寿蛋白质如胶原上积累，并介导这些蛋白质的交联，引起胶原病理生理学的变化，导致正常胶原基质重塑的破坏。研究了两种常用的晚期糖基化终产物前体3-脱氧葡萄糖醛酮和甲基乙二醛在胶原蛋白修饰和细胞外基质表达中的作用。甲基乙二醛交联基质上培养的成纤维细胞增加了胶原蛋白，活性TGF-β 1，β 1-整合素的表达，并减少Smad 7;而3-脱氧葡萄糖酮减少胶原蛋白，活性TGF-β 1，β 1-整合素，但增加Smad 7。纯化的胶原蛋白修饰的3-脱氧葡萄糖酮或甲基乙二醛具有不同的分子量;甲基乙二醛增加了约20 kDa的表观分子量，而3-脱氧葡萄糖酮没有。3-脱氧葡萄糖醛酮和甲基乙二醛在胶原蛋白表达上的差异提出了一个挑衅性的想法，即导致这些晚期糖基化终产物前体之一占优势的遗传或环境背景可能会在易感个体中沉淀纤维化或慢性伤口，特别是在糖尿病患者中。(C)2009爱思唯尔B.V，保留所有权利。
Advanced glycation endproducts accumulate on long-lived proteins such as collagens as a function of diet and age and mediate the cross-linking of those proteins causing changes in collagen pathophysiology resulting in the disruption of normal collagen matrix remodeling. Two commonly studied advanced glycation endproduct precursors 3-deoxyglucosone and methylglyoxal were investigated for their role in the modification of collagen and on extracellular matrix expression. Fibroblasts cultured on methylglyoxal cross-linked matrices increased the expression of collagen, active TGF-beta1, beta1-integrin, and decreased Smad7; whereas 3-deoxyglucosone decreased collagen, active TGF-beta1, beta1-integrin but increased Smad7. Purified collagen modified by 3-deoxyglucosone or methylglyoxal had different molecular weights; methylglyoxal increased the apparent molecular weight by approximately 20kDa, whereas 3-deoxyglucosone did not. The differences in collagen expression by 3-deoxyglucosone and methylglyoxal raise the provocative idea that a genetic or environmental background leading to the predominance of one of these advanced glycation endproduct precursors may precipitate a fibrotic or chronic wound in susceptible individuals, particularly in the diabetic. (C) 2009 Elsevier B.V, All rights reserved.