Fibrillin-containing microfibrils: structure and function in health and disease.
ABSTRACT Fibrillin-containing microfibrils are a unique class of connective tissue macromolecules whose critical contribution to the establishment and maintenance of diverse extracellular matrices was underlined by the recent linkage of their principal structural component fibrillin to Marfan syndrome, a heritable disorder with pleiotrophic connective tissue manifestations. The complexity of the structure: function relationships of these macromolecules was highlighted by the recent elucidation of the primary structure of fibrillin and characterisation of fibrillin mutations in Marfan patients. This review examines current understanding of the expression and assembly of fibrillin and describes new approaches which are now being applied to elucidate the many outstanding structural, organisational and functional aspects of the fibrillin-containing microfibrils.
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ABSTRACT: To determine the composition and investigate the elastin fiber system in the juxtacanalicular tissue adjacent to and between collector channel orifices in normal human eyes. Normal human eyes (71.0 ± 8.6 years; mean ± SD; n = 4) were perfusion fixed at low (10 mm Hg) and high pressure (20 mm Hg) with 3% paraformaldehyde/0.1 M phosphate buffer. Frontal serial sections were cut from paraffin blocks, and regions with and without collector channels were selected. Sections were stained using Weigert's resorcin-fuchsin stain with oxidation. Immunohistochemistry was performed using antibodies against elastin, fibrillin-1, and microfibrillar-associated protein-1/2. Elastin, elaunin, and oxytalan fibers were identified within the juxtacanalicular tissue of the inner and outer walls in low- and high-pressure eyes. These fibers were found at collector channel orifices, between collector channels, and within collector channel walls. Fibrillin-1 was located at the base and lateral edges of Schlemm's canal endothelial cells. Microfibrillar-associated protein-1/2 was found with elastin-like fibers at the base of Schlemm's canal endothelium cells, in the juxtacanalicular tissue, and in the uveal region. Elastin, elaunin, oxytalan, and elastin-associated proteins fibrillin-1 and microfibrillar-associated protein-1/2 were identified within the juxtacanalicular tissue of the inner and outer walls and within collector channel walls of human eyes perfused at low and high pressure. No differences in labeling patterns for elastin, elaunin, and oxytalan were found in the juxtacanalicular tissue adjacent to or between collector channel orifices. The elastin fiber system appears to have a significant role in the support and distensibility of the juxtacanalicular region under collector channels.Investigative ophthalmology & visual science 01/2011; 52(1):45-50. · 3.43 Impact Factor
Chapter: The Marfan Syndrome[Show abstract] [Hide abstract]
ABSTRACT: Marfan syndrome (MFS), a multisystem disorder of connective tissue, was described more than a century ago. Ground-breaking advances in the understanding of MFS were punctuated by the discovery of fibrillin, the identification of the FBN-1 as the causative gene, and the dissection of molecular pathogenesis through the creative use of animal models. The role of TGFb signaling in fibrillinopathies and related disorders is the most recent mechanistic development. Respiratory system involvement, although not as well characterized as the classic skeletal, ocular, and cardiac manifestations, can be clinically consequential. The lung manifestations of MFS may provide a mechanistic window not only on the pathobiology of the syndrome but also on other lung disorders with similar presentations. Keywords:Marfan’s syndrome-lung-fibrillin-FBN1-TGFBR 1-emphysema03/2010: pages 225-245;
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ABSTRACT: Force-bearing tissues such as blood vessels, lungs, and ligaments depend on the properties of elasticity and flexibility. The 10 to 12 nm diameter fibrillin microfibrils play vital roles in maintaining the structural integrity of these highly dynamic tissues and in regulating extracellular growth factors. In humans, defective microfibril function results in several diseases affecting the skin, cardiovascular, skeletal, and ocular systems. Despite the discovery of fibrillin-1 having occurred more than two decades ago, the structure and organization of fibrillin monomers within the microfibrils are still controversial. Recent structural data have revealed strategies by which fibrillin is able to maintain its architecture in dynamic tissues without compromising its ability to interact with itself and other cell matrix components. This review summarizes our current knowledge of microfibril structure, from individual fibrillin domains and the calcium-dependent tuning of pairwise interdomain interactions to microfibril dynamics, and how this relates to microfibril function in health and disease.Structure 02/2012; 20(2):215-25. · 5.99 Impact Factor