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弹性纤维形成的分子网络的最新进展。

Recent updates on the molecular network of elastic fiber formation.

机构信息

Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tsukuba 305-8577, Japan.

Graduate School of Life and Environmental Sciences, University of Tsukuba, Ibaraki 305-8577, Japan.

出版信息

Essays Biochem. 2019 Sep 13;63(3):365-376. doi: 10.1042/EBC20180052.

Abstract

Elastic fibers confer elasticity and recoiling to tissues and organs and play an essential role in induction of biochemical responses in a cell against mechanical forces derived from the microenvironment. The core component of elastic fibers is elastin (ELN), which is secreted as the monomer tropoelastin from elastogenic cells, and undergoes self-aggregation, cross-linking and deposition on to microfibrils, and assemble into insoluble ELN polymers. For elastic fibers to form, a microfibril scaffold (primarily formed by fibrillin-1 (FBN1)) is required. Numerous elastic fiber-associated proteins are involved in each step of elastogenesis and they instruct and/or facilitate the elastogenesis processes. In this review, we designated five proteins as key molecules in elastic fiber formation, including ELN, FBN1, fibulin-4 (FBLN4), fibulin-5 (FBLN5), and latent TGFβ-binding protein-4 (LTBP4). ELN and FBN1 serve as building blocks for elastic fibers. FBLN5, FBLN4 and LTBP4 have been demonstrated to play crucial roles in elastogenesis through knockout studies in mice. Using these molecules as a platform and expanding the elastic fiber network through the generation of an interactome map, we provide a concise review of elastogenesis with a recent update as well as discuss various biological functions of elastic fiber-associated proteins beyond elastogenesis .

摘要

弹性纤维赋予组织和器官弹性和回弹力,并在细胞对来自微环境的机械力的生化反应诱导中发挥重要作用。弹性纤维的核心成分是弹性蛋白 (ELN),它作为单体原弹性蛋白从弹性生成细胞分泌,并经历自我聚集、交联和沉积到微纤维上,并组装成不溶性 ELN 聚合物。为了形成弹性纤维,需要微纤维支架(主要由原纤维蛋白 1 (FBN1) 形成)。许多与弹性纤维相关的蛋白质参与弹性蛋白生成的每一步,它们指导和/或促进弹性蛋白生成过程。在这篇综述中,我们将五种蛋白质指定为弹性纤维形成的关键分子,包括 ELN、FBN1、纤连蛋白 4 (FBLN4)、纤连蛋白 5 (FBLN5) 和潜伏 TGFβ 结合蛋白 4 (LTBP4)。ELN 和 FBN1 是弹性纤维的构建块。通过在小鼠中进行基因敲除研究,已经证明 FBLN5、FBLN4 和 LTBP4 在弹性蛋白生成中发挥关键作用。使用这些分子作为平台,并通过生成相互作用图谱来扩展弹性纤维网络,我们提供了一个关于弹性蛋白生成的简洁综述,以及讨论了弹性纤维相关蛋白除了弹性蛋白生成之外的各种生物学功能。

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