In Situ Imaging of Tissue Remodeling with Collagen Hybridizing Peptides.
In Situ Imaging of Tissue Remodeling with Collagen Hybridizing Peptides.
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DOI：
10.1021/acsnano.7b03150
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发表时间：
2017-10-24
期刊：
影响因子：
17.1
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Hwang J;Huang Y;Burwell TJ;Peterson NC;Connor J;Weiss SJ;Yu SM;Li Y
胶原蛋白是几乎所有哺乳动物组织的主要结构成分，在发育状态和各种威胁生命的疾病(如癌症、心肌梗死和纤维化)中经历广泛的蛋白水解性重塑。虽然降解的胶原蛋白可能是组织损伤的重要标志，但使用传统工具很难检测和靶向。在这里，我们展示了一种设计的多肽(胶原杂交肽：CHP)，它特定地与降解的、未折叠的胶原链杂交，可以用于成像降解的胶原蛋白并告知各种组织中的组织重塑活动：用5-羧基荧光素和生物素标记的CHPs能够直接定位和量化从骨关节炎和心肌梗死到肾小球肾炎和肺纤维化等病理状态下的孤立组织中的胶原蛋白降解，以及与胚胎骨形成和皮肤老化相关的发育过程中的正常组织中的胶原蛋白降解。结果表明，胶原重塑水平与组织中变性胶原量之间存在普遍相关性，并表明CHP探针可以跨物种和胶原类型使用，不仅为病理学和发育生物学研究提供了一个通用的工具，而且为基于组织学的疾病诊断、分期和治疗筛选提供了一个通用的工具。本研究为进一步在不同动物模型中测试CHP作为鼻腔给药的靶向部分奠定了基础。
Collagen, the major structural component of nearly all mammalian tissues, undergoes extensive proteolytic remodeling during developmental states and a variety of life-threatening diseases such as cancer, myocardial infarction, and fibrosis. While degraded collagen could be an important marker of tissue damage, it is difficult to detect and target using conventional tools. Here, we show that a designed peptide (collagen hybridizing peptide: CHP), which specifically hybridizes to the degraded, unfolded collagen chains, can be used to image degraded collagen and inform tissue remodeling activity in various tissues: labeled with 5-carboxyfluorescein and biotin, CHPs enabled direct localization and quantification of collagen degradation in isolated tissues within pathologic states ranging from osteoarthritis and myocardial infarction to glomerulonephritis and pulmonary fibrosis, as well as in normal tissues during developmental programs associated with embryonic bone formation and skin aging. The results indicate the general correlation between the level of collagen remodeling and the amount of denatured collagen in tissue and show that the CHP probes can be used across species and collagen types, providing a versatile tool for not only pathology and developmental biology research but also histology-based disease diagnosis, staging, and therapeutic screening. This study lays the foundation for further testing CHP as a targeting moiety for theranostic delivery in various animal models.
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影响因子：
5.6
作者：
Boudko, S;Frank, S;Engel, J
通讯作者：
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影响因子：
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作者：
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DOI：
10.1007/bf00266843
发表时间：
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期刊：
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作者：
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通讯作者：
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