Analysis of dermal elastic fibers in the absence of fibulin-5 reveals potential roles for fibulin-5 in elastic fiber assembly.
Analysis of dermal elastic fibers in the absence of fibulin-5 reveals potential roles for fibulin-5 in elastic fiber assembly.
复制标题
DOI：
10.1016/j.matbio.2009.03.004
复制
发表时间：
2009-05
期刊：
影响因子：
6.9
通讯作者：
Davis, Elaine C.
中科院分区：
文献类型：
--
作者：
Choi, Jiwon;Bergdahl, Andreas;Zheng, Qian;Starcher, Barry;Yanagisawa, Hiromi;Davis, Elaine C.
纤维蛋白-5是一种66kda的模块化细胞外基质蛋白，定位于弹性纤维。尽管体外蛋白-蛋白结合研究表明，纤维蛋白-5结合了许多参与弹性纤维形成的蛋白，但纤维蛋白-5在弹性发生中的具体作用仍不清楚。为了更详细地分析纤维蛋白-5缺失情况下的弹性纤维组装，我们用电子显微镜（EM）检查了野生型和纤维蛋白-5基因敲除（Fbln5 - / -）小鼠的真皮。光镜显示Fbln5 - / -小鼠毛囊附近有明显正常的弹性纤维，其间真皮中没有弹性纤维，但电镜显示两个部位都有异常聚集的弹性纤维。弹性蛋白并没有被整合到微纤维支架中，而是以小球的形式出现在微纤维旁边。desmoine分析显示Fbln5−/−真皮中成熟交联弹性蛋白水平显著降低，然而，主要弹性纤维成分tropoelastin和fibrin -1的基因表达水平未受影响。在此基础上，利用赖氨酸氧化酶样-1 （LOXL-1）结构域特异性抗体研究了tropoelastin交联的性质。用一种针对n端前肽的抗体进行免疫定位，发现Fbln5−/−真皮层中有丰富的染色，而野生型真皮层中没有染色。总的来说，这些结果表明纤维蛋白-5在弹性形成中有两个以前未被认识到的功能；首先，限制对流层弹性蛋白单体和/或凝聚的聚集程度，并有助于将弹性蛋白结合到微纤维束中，其次，可能有助于LOXL-1的激活。
Fibulin-5 is a 66 kDa modular, extracellular matrix protein that localizes to elastic fibers. Although in vitro protein-protein binding studies have shown that fibulin-5 binds many proteins involved in elastic fiber formation, the specific role of fibulin-5 in elastogenesis remains unclear. To provide a more detailed analysis of elastic fiber assembly in the absence of fibulin-5, the dermis of wild-type and fibulin-5 gene knockout (Fbln5−/−) mice was examined with electron microscopy (EM). Although light microscopy showed apparently normal elastic fibers near the hair follicles and the absence of elastic fibers in the intervening dermis of the Fbln5−/− mouse, EM revealed the presence of aberrantly assembled elastic fibers in both locales. Instead of the elastin being incorporated into the microfibrillar scaffold, the elastin appeared as globules juxtaposed to the microfibrils. Desmosine analysis showed significantly lower levels of mature cross-linked elastin in the the Fbln5−/− dermis, however, gene expression levels for tropoelastin and fibrillin-1, the major elastic fiber components, were unaffected. Based on these results, the nature of tropoelastin cross-linking was investigated using domain specific antibodies to lysyl oxidase like-1 (LOXL-1). Immunolocalization with an antibody to the N-terminal pro-peptide, which is cleaved to generate the active enzyme, revealed abundant staining in the Fbln5−/− dermis and no staining in the wild-type dermis. Overall, these results suggest two previously unrecognized functions for fibulin-5 in elastogenesis; first, to limit the extent of aggregation of tropoelastin monomers and/or coacervates and aid in the incorporation of elastin into the microfibril bundles, and second, to potentially assist in the activation of LOXL-1.
登录
查看更多内容
影响因子：
5.6
作者：
Dabovic, Branka;Chen, Yan;Rifkin, Daniel B.
通讯作者：
Rifkin, Daniel B.
影响因子：
4.8
作者：
Broekelmann, TJ;Kozel, BA;Mecham, RP
通讯作者：
Mecham, RP
影响因子：
2.9
作者：
Bellingham, CM;Lillie, MA;Keeley, FW
通讯作者：
Keeley, FW
影响因子：
30.8
作者：
Liu, XQ;Zhao, Y;Li, TS
通讯作者：
Li, TS
影响因子：
3.4
作者：
Buechner, SA;Itin, P
通讯作者：
Itin, P