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In Situ Imaging of Tissue Remodeling with Collagen Hybridizing Peptides
ACS Nano ( IF 15.8 ) Pub Date : 2017-09-18 00:00:00 , DOI: 10.1021/acsnano.7b03150
Jeongmin Hwang 1 , Yufeng Huang 2 , Timothy J. Burwell 3 , Norman C. Peterson 3 , Jane Connor 3 , Stephen J. Weiss 4 , S. Michael Yu 1 , Yang Li 1
Affiliation  

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.

中文翻译:

胶原蛋白杂交肽对组织重塑的原位成像

胶原蛋白是几乎所有哺乳动物组织的主要结构组成部分,在发育状态和各种威胁生命的疾病(例如癌症,心肌梗塞和纤维化)中经历了广泛的蛋白水解重塑。尽管降解的胶原蛋白可能是组织损伤的重要标志,但使用常规工具很难检测和靶向。在这里,我们显示了设计的肽(胶原蛋白杂交肽:CHP)可以与降解的,未折叠的胶原蛋白链特异性杂交,可用于成像降解的胶原蛋白并告知各种组织的组织重塑活性:用5-羧基荧光素和生物素标记,CHP能够直接定位和量化病理状态(包括骨关节炎,心肌梗塞,肾小球肾炎和肺纤维化)以及与胚胎骨形成和皮肤老化相关的正常组织中正常组织中孤立组织中的胶原蛋白降解。结果表明胶原重塑水平和组织中变性胶原含量之间的一般相关性,并表明CHP探针可用于各种物种和胶原类型,不仅为病理学和发育生物学研究提供了多功能工具,而且为组织学提供了多功能的工具的疾病诊断,分期和治疗性筛查。这项研究为进一步测试CHP作为在各种动物模型中进行治疗治疗的靶向部分奠定了基础。
更新日期:2017-09-19
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