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费尔·缪尔讲座:体外和体内的胶原纤维形成

Fell Muir Lecture: Collagen fibril formation in vitro and in vivo.

作者信息

Kadler Karl E

机构信息

Faculty of Biology, Medicine and Health, Wellcome Trust Centre for Cell-Matrix Research, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.

出版信息

Int J Exp Pathol. 2017 Feb;98(1):4-16. doi: 10.1111/iep.12224. Epub 2017 May 16.

DOI:10.1111/iep.12224
PMID:28508516
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5447863/
Abstract

It is a great honour to be awarded the Fell Muir Prize for 2016 by the British Society of Matrix Biology. As recipient of the prize, I am taking the opportunity to write a minireview on collagen fibrillogenesis, which has been the focus of my research for 33 years. This is the process by which triple helical collagen molecules assemble into centimetre-long fibrils in the extracellular matrix of animals. The fibrils appeared a billion years ago at the dawn of multicellular animal life as the primary scaffold for tissue morphogenesis. The fibrils occur in exquisite three-dimensional architectures that match the physical demands of tissues, for example orthogonal lattices in cornea, basket weaves in skin and blood vessels, and parallel bundles in tendon, ligament and nerves. The question of how collagen fibrils are formed was posed at the end of the nineteenth century. Since then, we have learned about the structure of DNA and the peptide bond, understood how plants capture the sun's energy, cloned animals, discovered antibiotics and found ways of editing our genome in the pursuit of new cures for diseases. However, how cells generate tissues from collagen fibrils remains one of the big unsolved mysteries in biology. In this review, I will give a personal account of the topic and highlight some of the approaches that my research group are taking to find new insights.

摘要

非常荣幸获得英国基质生物学学会颁发的2016年费尔·缪尔奖。作为该奖项的获得者,我借此机会撰写一篇关于胶原蛋白原纤维形成的小型综述,这一直是我33年来的研究重点。这是一个三螺旋胶原蛋白分子在动物细胞外基质中组装成厘米长原纤维的过程。这些原纤维在十亿年前多细胞动物生命诞生之初就出现了,是组织形态发生的主要支架。原纤维呈现出精美的三维结构,与组织的物理需求相匹配,例如角膜中的正交晶格、皮肤和血管中的篮状编织结构以及肌腱、韧带和神经中的平行束状结构。胶原蛋白原纤维如何形成的问题在19世纪末就被提出来了。从那时起,我们了解了DNA的结构和肽键,明白了植物如何捕获太阳能,克隆了动物,发现了抗生素,并找到了编辑我们基因组以寻求新疾病治疗方法的途径。然而,细胞如何从胶原蛋白原纤维生成组织仍然是生物学中尚未解决的重大谜团之一。在这篇综述中,我将个人阐述这个主题,并重点介绍我的研究小组为获得新见解所采用的一些方法。

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Loss of Type I Collagen Telopeptide Lysyl Hydroxylation Causes Musculoskeletal Abnormalities in a Zebrafish Model of Bruck Syndrome.I型胶原蛋白端肽赖氨酰羟化的缺失在布鲁克综合征斑马鱼模型中导致肌肉骨骼异常。
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