PDF(Pubmed)
Abstract：
Fibrillin-1 (FBN1) is a large, cysteine-rich, calcium binding extracellular matrix glycoprotein encoded by FBN1 gene. It serves as a structural component of microfibrils and provides force-bearing mechanical support in elastic and nonelastic connective tissue. As such, mutations in the FBN1 gene can cause a wide variety of genetic diseases such as Marfan syndrome, an autosomal dominant disorder characterized by ocular, skeletal and cardiovascular abnormalities. FBN1 also interacts with numerous microfibril-associated proteins, growth factors and cell membrane receptors, thereby mediating a wide range of biological processes such as cell survival, proliferation, migration and differentiation. Dysregulation of FBN1 is involved in the pathogenesis of many human diseases, such as cancers, cardiovascular disorders and kidney diseases. Paradoxically, both depletion and overexpression of FBN1 upregulate the bioavailability and signal transduction of TGF-β via distinct mechanisms in different settings. In this review, we summarize the structure and expression of FBN1 and present our current understanding of the functional role of FBN1 in various human diseases. This knowledge will allow to develop better strategies for therapeutic intervention of FBN1 related diseases.
摘要：
纤溶蛋白-1(FBN1)是一种大型的,富含半胱氨酸,FBN1基因编码的钙结合细胞外基质糖蛋白。它作为微纤维的结构成分，并在弹性和非弹性结缔组织中提供受力机械支撑。因此，FBN1基因的突变可引起多种遗传疾病，如马凡氏综合征，一种以眼部为特征的常染色体显性疾病，骨骼和心血管异常。FBN1还与许多微原纤维相关蛋白相互作用，生长因子和细胞膜受体，从而介导广泛的生物过程，如细胞存活，扩散,迁移和分化。FBN1的失调与许多人类疾病的发病机制有关。比如癌症，心血管疾病和肾脏疾病。矛盾的是,在不同的环境中,FBN1的缺失和过表达均通过不同的机制上调TGF-β的生物利用度和信号转导。在这次审查中,我们总结了FBN1的结构和表达，并介绍了我们目前对FBN1在各种人类疾病中的功能作用的理解。这些知识将有助于制定更好的治疗性干预FBN1相关疾病的策略。
