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.
[Show abstract] [Hide abstract]
ABSTRACT: Abstract There is increasing evidence for a progressive extracellular matrix change in rotator cuff disease progression. Directly surrounding the cell is the pericellular matrix, where assembly of matrix aggregates typically occurs making it critical in the response of tendon cells to pathological conditions. Studies in animal models have identified type VI collagen, fibrillin-1 and elastin to be located in the pericellular matrix of tendon and contribute in maintaining the structural and biomechanical integrity of tendon. However, there have been no reports on the localization of these proteins in human tendon biopsies. This study aimed to characterise the distribution of these ECM components in human rotator cuffs and gain greater insight into the relationship of pathology to tear size by analyzing the distribution and expression profiles of these ECM components. Confocal microscopy confirmed the localization of these structural molecules in the pericellular matrix of the human rotator cuff. Tendon degeneration led to an increased visibility of these components with a significant disorganization in the distribution of type VI collagen. At the genetic level, an increase in tear size was linked to an increased transcription of type VI collagen and fibrillin-1 with no significant alteration in the elastin levels. This is the first study to confirm the localization of type VI collagen, elastin, and fibrillin-1 in the pericellular region of human supraspinatus tendon and assesses the effect of tendon degeneration on these structures, thus providing a useful insight into the composition of human rotator cuff tears which can be instrumental in predicting disease prognosis.Connective Tissue Research 08/2014; 55(5-6):1-21. DOI:10.3109/03008207.2014.959119 · 1.98 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Marfan syndrome is a disorder of connective tissue associated with progressive dilation of the aorta and potential risk for aortic dissection. Women with Marfan syndrome who are, or wish to become, pregnant represent a unique and challenging patient population due to a risk for accelerated aortic growth and aortic dissection during pregnancy. Risk for aortic complications during pregnancy is related to the dimensions of the ascending aorta. Women with an aortic diameter ≥4.5 cm at the start of pregnancy are at higher risk for aortic dissection, and an aortic dimension >4.0 cm is considered a relative contraindication to pregnancy in the setting of Marfan syndrome.Archives of Gynecology and Obstetrics 06/2014; 290(4). DOI:10.1007/s00404-014-3307-4 · 1.28 Impact Factor
Article: Corneal Stroma Microfibrils.[Show abstract] [Hide abstract]
ABSTRACT: Elastic tissue was first described well over a hundred years ago and has since been identified in nearly every part of the body. In this review, we examine elastic tissue in the corneal stroma with some mention of other ocular structures which have been more thoroughly described in the past. True elastic fibers consist of an elastin core surrounded by fibrillin microfibrils. However, the presence of elastin fibers is not a requirement and some elastic tissue is comprised of non-elastin-containing bundles of microfibrils. Fibers containing a higher relative amount of elastin are associated with greater elasticity and those without elastin, with structural support. Recently it has been shown that the microfibrils, not only serve mechanical roles, but are also involved in cell signaling through force transduction and the release of TGF-β. A well characterized example of elastin-free microfibril bundles (EFMBs) is found in the ciliary zonules which suspend the crystalline lens in the eye. Through contraction of the ciliary muscle they exert enough force to reshape the lens and thereby change its focal point. It is believed that the molecules comprising these fibers do not turn-over and yet retain their tensile strength for the life of the animal. The mechanical properties of the cornea (strength, elasticity, resiliency) would suggest that EFMBs are present there as well. However, many authors have reported that, although present during embryonic and early postnatal development, EFMBs are generally not present in adults. Serial-block-face imaging with a scanning electron microscope enabled 3D reconstruction of elements in murine corneas. Among these elements were found fibers that formed an extensive network throughout the cornea. In single sections these fibers appeared as electron dense patches. Transmission electron microscopy provided additional detail of these patches and showed them to be composed of fibrils (∼10nm diameter). Immunogold evidence clearly identified these fibrils as fibrillin EFMBs and EFMBs were also observed with TEM (without immunogold) in adult mammals of several species. Evidence of the presence of EFMBs in adult corneas will hopefully pique an interest in further studies that will ultimately improve our understanding of the cornea's biomechanical properties and its capacity to repair. Copyright © 2015. Published by Elsevier Ltd.Experimental Eye Research 01/2015; 132. DOI:10.1016/j.exer.2015.01.014 · 3.02 Impact Factor