The extracellular matrix glycoprotein fibrillin-1 in health and disease

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.

Genetic Manipulation of Caveolin-1 in the Mouse Model of Marfan Syndrome Associated Aortic Root Aneurysm: Effects on Endothelial and Smooth Muscle Function

“…MFS has an estimated prevalence of 1 in 3000-5000 with no biological sex or ethnic bias 1,2 . Fbn1 is one of the major constituents of extracellular microfibrils found in connective tissues that provides scaffolding support for the formation and maturation of elastin fibers, thus, supporting the integrity and elasticity of connective tissues 3,4 . In addition to its structural role, Fbn1 can regulate multiple signaling molecules within the extracellular matrix (ECM), particularly, the activity of the cytokine transforming growth factor beta (TGF-β) through its ability to sequester the latent form of TGF-β within the ECM [5][6][7] .…”