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首页> 外文期刊>Biochemical Pharmacology >Biochemical characterization of the binding of cyclic RGDyK to hepatic stellate cells.
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Biochemical characterization of the binding of cyclic RGDyK to hepatic stellate cells.

机译：环状RGDyK与肝星状细胞结合的生化特征。

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摘要

Activated hepatic stellate cells (HSCs) play a crucial role in the development of liver fibrosis. Noninvasive monitoring of the activation of HSCs has been challenging due to the lack of specific receptors or motifs on the cells. The present study provides the evidence that integrin alpha v beta 3 expressed on HSCs is a biomarker reflecting the activation of HSCs. Solid-phase synthesis of cRGDyK (Arg-Gly-Asp-(D)Tyr-Lys) peptide and FAM-conjugated peptide were employed for binding to integrin alpha v beta 3. The increased expression of integrin alpha v and beta 3 at mRNA and protein levels was detected during HSC activation. The affinity of cRGDyK to integrin alpha v beta 3 was examined by both radioligand binding assay and FAM-conjugated peptide binding measurements. Quantitative RT-PCR and Western blotting showed a less dramatic, but significant increase in alpha v and beta 3 integrin mRNA and protein expression following activation of rat HSCs. Radioiodinated cRGDyK binds to both purified and membrane-bound integrin alpha v beta 3 with high affinity in a dissociable manner. FAM-conjugated cRGDyK was coupled to activated HSCs in a time- and dose-dependent, receptor-mediated manner. Activated HSCs express sufficient number of integrin alpha v beta 3 receptor. cRGDyK peptide binds to both purified and membrane-bound integrin alpha v beta 3 with high affinity in a reversible fashion. Thus, the cRGDyK peptide represented a new agent potentially useful for the diagnosis of liver fibrosis.
机译：活化的肝星状细胞（HSC）在肝纤维化的发展中起关键作用。由于细胞上缺乏特异性受体或基序，对HSCs活化进行非侵入性监测一直具有挑战性。本研究提供的证据表明，在HSC上表达的整合素αv beta 3是反映HSC激活的生物标志物。 cRGDyK（Arg-Gly-Asp-（D）Tyr-Lys）肽和FAM缀合肽的固相合成用于结合整联蛋白αv beta 3。在HSC激活过程中检测到蛋白质水平。通过放射性配体结合测定和FAM-缀合的肽结合测量，检查了cRGDyK对整联蛋白αv beta 3的亲和力。定量RT-PCR和Western印迹显示大鼠HSC激活后，αv和β3整联蛋白mRNA和蛋白表达的戏剧性降低，但显着增加。放射性碘化的cRGDyK以可分离的方式高亲和力与纯化的和膜结合的整联蛋白αv beta 3结合。 FAM偶联的cRGDyK以时间和剂量依赖性，受体介导的方式与活化的HSC偶联。活化的HSC表达足够数量的整联蛋白αv beta 3受体。 cRGDyK肽可逆地以高亲和力与纯化的和膜结合的整联蛋白αv beta 3结合。因此，cRGDyK肽代表了一种可能对肝纤维化诊断有用的新药物。

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