Fibulins: a versatile family of extracellular matrix proteins

Timpl, Rupert; Sasaki, Takako; Kostka, Günter; Chu, Mon‐Li

doi:10.1038/nrm1130

Cited by 452 publications

(416 citation statements)

References 90 publications

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“…However, these models are complex and not completely in agreement and no details for the outflow pathway have been established. (Aspberg et al 1999;Trask et al 1999;Trask et al 2000;Olin et al 2001;Isogai et al 2002;Kielty et al 2002a;Kielty et al 2002b;Segade et al 2002;Timpl et al 2003;Kielty et al 2005) Several models could be proposed that would link this system to the ECM components that may be involved in the outflow resistance and to specific cellattachment components.…”

Section: Elastin and Microfibrilsmentioning

confidence: 99%

Extracellular matrix in the trabecular meshwork

Acott

Kelley

2008

Experimental Eye Research

424

443

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The extracellular matrix (ECM) of the trabecular meshwork (TM) is thought to be important in regulating intraocular pressure (IOP) in both normal and glaucomatous eyes. IOP is regulated primarily by a fluid resistance to aqueous humor outflow. However, neither the exact site nor the identity of the normal resistance to aqueous humor outflow has been established. Whether the site and nature of the increased outflow resistance, which is associated with open-angle glaucoma, is the same or different from the normal resistance is also unclear.The ECMs of the TM beams, juxtacanalicular region (JCT) and Schlemm's canal (SC) inner wall are comprised of fibrillar and non-fibrillar collagens, elastin-containing microfibrils, matricellular and structural organizing proteins, glycosaminoglycans (GAGs) and proteoglycans. Both basement membranes and stromal ECM are present in the TM beams and JCT region. Cell adhesion proteins, cell surface ECM receptors and associated binding proteins are also present in the beams, JCT and SC inner wall region.The outflow pathway ECM is relatively dynamic, undergoing constant turnover and remodeling. Regulated changes in enzymes responsible for ECM degradation and biosynthetic replacement are observed. IOP homeostasis, triggered by pressure changes or mechanical stretching of the TM, appears to involve ECM turnover. Several cytokines, growth factors and drugs, which affect the outflow resistance, change ECM component expression, mRNA alternative splicing, cellular cytoskeletal organization or all of these. Changes in ECM associated with open-angle glaucoma have been identified.

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Section: Elastin and Microfibrilsmentioning

confidence: 99%

Extracellular matrix in the trabecular meshwork

Acott

Kelley

2008

Experimental Eye Research

424

443

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“…Fibulins are 50-200 kDa in size (Timpl et al, 2003) and have a series of calcium binding EGF-like domains followed by a carboxyterminal fibulin-like domain (Argraves et al, 2003). There are five members of the fibulin family.…”

Section: Fibulinsmentioning

confidence: 99%

New insights into elastic fiber assembly

Wagenseil

Mecham

2007

Birth Defects Research Pt C

357

354

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Elastic fibers provide recoil to tissues that undergo repeated stretch, such as the large arteries and lung. These large extracellular matrix (ECM) structures contain numerous components, and our understanding of elastic fiber assembly is changing as we learn more about the various molecules associated with the assembly process. The main components of elastic fibers are elastin and microfibrils. Elastin makes up the bulk of the mature fiber and is encoded by a single gene. Microfibrils consist mainly of fibrillin, but also contain or associate with proteins such as microfibril associated glycoproteins (MAGPs), fibulins, and EMILIN-1. Microfibrils were thought to facilitate alignment of elastin monomers prior to cross-linking by lysyl oxidase (LOX). We now know that their role, as well as the overall assembly process, is more complex. Elastic fiber formation involves elaborate spatial and temporal regulation of all of the involved proteins and is difficult to recapitulate in adult tissues. This report summarizes the known interactions between elastin and the microfibrillar proteins and their role in elastic fiber assembly based on in vitro studies and evidence from knockout mice. We also propose a model of elastic fiber assembly based on the current data that incorporates interactions between elastin, LOXs, fibulins and the microfibril, as well as the pivotal role played by cells in structuring the final functional fiber. Birth Defects Research (Part C) 81:229-240,

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“…In SFD point mutations, eight of which have been identified, in the Timp-3 gene result in unpaired cysteines in the c-terminal end of the expressed protein. ML arises from a single Arg345Trp mutation in Fibulin 3, also an extracellular protein with a number of EGF-like repeats, leading to misfolding of the protein (Timpl et al, 2003). SFD is characterized by thickening of Bruch's membrane, deposition of lipofuscin like material, atrophy of the RPE and subretinal neovascularisation.…”

Section: Mitochondrial Ros Systems and Maculopathymentioning

confidence: 99%

Mitochondrial function and redox control in the aging eye: Role of MsrA and other repair systems in cataract and macular degenerations

Brennan¹,

Kantorow²

2009

Experimental Eye Research

164

141

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Oxidative stress occurs when the level of prooxidants exceeds the level of antioxidants in cells resulting in oxidation of cellular components and consequent loss of cellular function. Oxidative stress is implicated in wide range of age related disorders including Alzheimer's disease, Parkinson's disease amyotrophic lateral sclerosis (ALS), Huntington's disease and the aging process itself (Lin and Beal, 2006). In the anterior segment of the eye, oxidative stress has been linked to lens cataract (Truscott, 2005) and glaucoma (Tezel, 2006) while in the posterior segment of the eye oxidative stress has been associated with macular degeneration (Hollyfield et al., 2008). Key to many oxidative stress conditions are alterations in the efficiency of mitochondrial respiration resulting in superoxide (O 2 -) production. Superoxide production precedes subsequent reactions that form potentially more dangerous reactive oxygen species (ROS) species such as the hydroxyl radical (˙OH), hydrogen peroxide (H 2 O 2 ) and peroxynitrite (OONO -). The major source of ROS in the mitochondria, and in the cell overall, is leakage of electrons from complexes I and III of the electron transport chain. It is estimated that 0.2-2% of oxygen taken up by cells is converted to ROS, through mitochondrial superoxide generation, by the mitochondria (Hansford et al., 1997). Generation of superoxide at complex I and III has been shown to occur at both the matrix side of the inner mitochondrial membrane and the cytosolic side of the membrane (Kakkar and Singh 2007). While exogenous sources of ROS such as UV light, visible light, ionizing radiation, chemotherapeutics, and environmental toxins may contribute to the oxidative milieu, mitochondria are perhaps the most significant contribution to ROS production affecting the aging process. In addition to producing ROS, mitochondria are also a target for ROS which in turn reduces mitochondrial efficiency and leads to the generation of more ROS in a vicious self-destructive cycle. Consequently, the mitochondria have evolved a number of antioxidant and key repair systems to limit the damaging potential of free oxygen radicals and to repair damaged proteins (Figure 1.0). The aging eye appears to be at considerable risk from oxidative stress. This review will outline the potential role of mitochondrial function and redox balance in age-related eye diseases, and detail how the methionine sulfoxide reductase (Msr)

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Fibulins: a versatile family of extracellular matrix proteins

Cited by 452 publications

References 90 publications

Extracellular matrix in the trabecular meshwork

Extracellular matrix in the trabecular meshwork

New insights into elastic fiber assembly

Mitochondrial function and redox control in the aging eye: Role of MsrA and other repair systems in cataract and macular degenerations

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