Beta 2-microglobulin modified with advanced glycation end products modulates collagen synthesis by human fibroblasts.
Beta 2-microglobulin modified with advanced glycation end products modulates collagen synthesis by human fibroblasts.
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DOI：
10.1046/j.1523-1755.1998.00882.x
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发表时间：
1998-05
影响因子：
19.6
通讯作者：
William F. Owen;Fan Fan Hou-Fan;Robert O. Stuart;Jonathan Kay;Joshua A. Boyce;Glenn M. Chertow;A. Schmidt
中科院分区：
文献类型：
--
作者：
William F. Owen;Fan Fan Hou-Fan;Robert O. Stuart;Jonathan Kay;Joshua A. Boyce;Glenn M. Chertow;A. Schmidt
β 2-微球蛋白淀粉样变性（A β 2 m）是长期透析患者的严重并发症。晚期糖基化终产物修饰的β 2-微球蛋白（β 2 m-AGE）是A β 2 m中淀粉样蛋白的主要成分。目前还不完全清楚β 2 m-AGE是否在A β 2 m的发病机制中起积极作用，或者它的存在是否是疾病的继发事件。β 2-微球蛋白淀粉样蛋白主要位于富含胶原蛋白的肌腱和骨关节结构中，并且局部成纤维细胞构成胶原蛋白合成和代谢的主要细胞群。最近在人成纤维细胞上鉴定的AGE结合蛋白导致了这样的假设，即成纤维细胞可能是β 2 m-AGE的生物学作用的靶点。本研究表明，两个人成纤维细胞系暴露于β 2 m-AGE 72小时后，I型前胶原mRNA和I型胶原合成减少。使用AGE修饰的白蛋白观察到类似的结果。抗AGE受体α-SMA的抗体减弱了这种合成的减少，表明这种反应部分由α-SMA介导。此外，抗表皮生长因子（EGF）的抗体减弱了β 2 m-AGE诱导的I型前胶原mRNA和I型胶原的减少，表明EGF起着中间因子的作用。这些发现支持了β 2 m-AGE通过涉及成纤维细胞增殖的途径和至少一种插入的介质生长因子EGF积极参与结缔组织和骨重塑的假设。
Beta 2-microglobulin amyloidosis (A beta 2m) is a serious complication for patients undergoing long-term dialysis. beta 2-microglobulin modified with advanced glycation end products (beta 2m-AGE) is a major component of the amyloid in A beta 2m. It is not completely understood whether beta 2m-AGE plays an active role in the pathogenesis of A beta 2m, or if its presence is a secondary event of the disease. beta 2-microglobulin amyloid is mainly located in tendon and osteo-articular structures that are rich in collagen, and local fibroblasts constitute the principal cell population in the synthesis and metabolism of collagen. Recent identification of AGE binding proteins on human fibroblasts lead to the hypothesis that the fibroblast may be a target for the biological action of beta 2m-AGE. The present study demonstrated that two human fibroblast cell lines exhibited a decrease in procollagen type I mRNA and type I collagen synthesis after exposure to beta 2m-AGE for 72 hours. Similar results were observed using AGE-modified albumin. Antibody against the RAGE, the receptor for AGE, attenuated this decrease in synthesis, indicating that the response was partially mediated by RAGE. In addition, antibody against epidermal growth factor (EGF) attenuated the decrease in type I procollagen mRNA and type I collagen induced by beta 2m-AGE, suggesting that EGF acts as an intermediate factor. These findings support the hypothesis that beta 2m-AGE actively participates in connective tissue and bone remodeling via a pathway involving fibroblast RAGE, and at least one interposed mediator, the growth factor EGF.