Structure and composition of the elastin fibre in normal and pathological conditions

Baccarani-Contri, M.; Fornieri, C.; Mori, G.; Quaglino, Daniela

doi:10.1016/0968-4328(93)90016-t

Cited by 34 publications

(24 citation statements)

References 72 publications

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“…It has been classically proposed that the microfibrillar components of the elastic fibers constitute a template which precedes elastin deposition (see Clearly et al, 1981;Pasquali-Ronchetti et al, 1993). In this study, although fibrillin and emilin…”

Section: Second Periodmentioning

confidence: 60%

Elastic extracellular matrix of the embryonic chick heart: An immunohistological study using laser confocal microscopy

Hurlé

Kitten

Sakai

et al. 1994

Developmental Dynamics

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The "elastic matrix" constitutes a specialized component of the extracellular matrix which confers resiliency to tissues and organs subjected to repeated deformations. The role of the elastic matrix in living organisms appears to be of key importance since diseases characterized by expression of defective inherited genes which encode components of the elastic matrix lead to premature death. While the elastic matrix of adult organs has received a great deal of attention, little is known about when it first appears in embryonic tissues or its possible role in developing organs. In the present study we have performed an immunohistochemical study of the distribution of elastin and three additional components often associated with elastic matrices in adult tissues (i.e., fibrillin, emilin, and type VI collagen) during the development of the chicken embryonic heart. The threedimensional arrangement of these components was established through the observation of wholemount specimens with scanning laser confocal microscopy. Our results revealed three different periods of heart development regarding the composition of the elastic matrix. Prior to stage 21 the embryonic heart lacks elastin but exhibits a matrix scaffold of fibrillin and emilin associated with the endocardium and the developing cardiac jelly. Between stages 22 and 29 the heart shows a transient elastic scaffold in the outflow tract which contains elastin, fibrillin, and emilin. Elastin-positive fibrillar material is also observed during these stages in the base of the atrioventricular cushion adjacent to the myocardial wall. In addition, emilin-positive material appears to be associated with the zones of formation of ventricular trabeculae. Collagen type VI was not detected during these early stages. From stage 30 to stage 40 a progressive modification of the pattern of distribution of elastin, fibrillin, emilin, and collagen type VI is observed in association with the formation of the definitive four-chambered heart. The distribution of the elastic scaffold in the outflow tract appears to be rearranged and becomes restricted to the roots of the main arteries. Each of the components studied here is also deposited at increasing levels in the developing valvular appa-ratus including the valve leaflets and the chordae tendinea. The components are also present in the subendocardial space where they form aligned fibrillar tracts, an arrangement suggestive of a role in ventricular contractile function. The epicardium constitutes an additional region of elastic matrix deposition during these later stages and contains elastic, fibrillin, and collagen type VI. Finally, during the later stages the intramyocardial matrix (''myocardial interstitium") is formed and characterized by an abundance of collagen type VI, emilin, and fibrillin but lacks elastin-positive material. This study suggests that during cardiac development there is not a fixed composition of the so-called "elastic matrix.'' Rather, combinations of the different components of the elastic matrice...

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Section: Second Periodmentioning

confidence: 60%

Elastic extracellular matrix of the embryonic chick heart: An immunohistological study using laser confocal microscopy

Hurlé

Kitten

Sakai

et al. 1994

Developmental Dynamics

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“…Unfortunately, the experimental requirements of the procedures, which are confluent cultures at the start of the experiment and a duration of at least 72 h of hypoxic incubation, excluded siRNA from analysis of endogenous E-cadherin because of low transfection efficiencies of the siRNA. For this reason, we referred to treatment with established pharmacological inhibitors of lysyl oxidases (40,52) (Fig. 6, C and D).…”

Section: E-cadherin Expression Is Lost Under Hypoxic Conditions Whicmentioning

confidence: 99%

The Lysyl Oxidases LOX and LOXL2 Are Necessary and Sufficient to Repress E-cadherin in Hypoxia

Schietke

Warnecke

Wacker

et al. 2010

Journal of Biological Chemistry

225

174

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Hypoxia has been shown to promote tumor metastasis and lead to therapy resistance. Recent work has demonstrated that hypoxia represses E-cadherin expression, a hallmark of epithelial to mesenchymal transition, which is believed to amplify tumor aggressiveness. The molecular mechanism of E-cadherin repression is unknown, yet lysyl oxidases have been implicated to be involved. Gene expression of lysyl oxidase (LOX) and the related LOX-like 2 (LOXL2) is strongly induced by hypoxia. In addition to the previously demonstrated LOX, we characterize LOXL2 as a direct transcriptional target of HIF-1. We demonstrate that activation of lysyl oxidases is required and sufficient for hypoxic repression of E-cadherin, which mediates cellular transformation and takes effect in cellular invasion assays. Our data support a molecular pathway from hypoxia to cellular transformation. It includes up-regulation of HIF and subsequent transcriptional induction of LOX and LOXL2, which repress E-cadherin and induce epithelial to mesenchymal transition. Lysyl oxidases could be an attractive molecular target for cancers of epithelial origin, in particular because they are partly extracellular.Constant availability of molecular oxygen is crucial for the structure and function of any mammalian cell. Therefore, cellular responses to reduced oxygen tensions (hypoxia) play an important role in development and many aspects of physiological homeostasis. Many important disease processes, including ischemic vascular diseases and cancer, involve reduced tissue oxygenation, and cellular adaptation to this is implicated in disease progression and clinical outcome. The hypoxia-inducible transcription factor (HIF) 2 is a central mechanism responding to low cellular oxygenation and mediates a variety of systemic and local adaptive responses, including the control of red cell production, regulation of angiogenesis, modulation of vascular tone, enhancement of glycolysis, and cellular glucose uptake (for a review, see Refs. 1-3). HIF consists of a heterodimer of ␣-and ␤-subunits, both being basic helix-loop-helix-Per Arnt Sim domain proteins. Whereas HIF␤ is constitutively expressed, HIF␣ subunits are unstable and inversely correlated to the availability of molecular oxygen. At least two oxygen-regulated isoforms of HIF␣ have been identified, HIF-1␣ and HIF-2␣, sharing a high degree of sequence homology and a similar domain structure (4). Regulation of HIF is primarily governed by oxygen-dependent hydroxylation of its HIF␣ subunits, which influences protein stability and transcriptional activity.Growth and behavior of tumor cells is strongly dependent on their microenvironment, where hypoxia is both a stress factor and an important signal (for a review, see Refs. 5 and 6). Dating back to 1927, Otto Warburg had already described that tumor cells have a much increased utilization of the glycolytic pathway (7). Since then, a number of studies have established that indeed HIF is necessary to activate glycolysis in tumor cells in order to maintain energy homeosta...

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“…Elastin is an ECM protein present in all connective tissues of vertebrates (14), rendering essential elasticity and resilience to aorta, lung, ligament, and skin subjected to repeated physiological stresses (15). Long thought to be purely mechanical, considerable evidence has now emerged regarding its physiological significance (16), for example, in vascular morphogenesis (17,18) and homeostasis (19) and in regulating cell functions (16).…”

Section: Resultsmentioning

confidence: 99%

Ferroelectric switching of elastin

Liu

Cai

Zelisko

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Ferroelectricity has long been speculated to have important biological functions, although its very existence in biology has never been firmly established. Here, we present compelling evidence that elastin, the key ECM protein found in connective tissues, is ferroelectric, and we elucidate the molecular mechanism of its switching. Nanoscale piezoresponse force microscopy and macroscopic pyroelectric measurements both show that elastin retains ferroelectricity at 473 K, with polarization on the order of 1 μC/cm 2 , whereas coarse-grained molecular dynamics simulations predict similar polarization with a Curie temperature of 580 K, which is higher than most synthetic molecular ferroelectrics. The polarization of elastin is found to be intrinsic in tropoelastin at the monomer level, analogous to the unit cell level polarization in classical perovskite ferroelectrics, and it switches via thermally activated cooperative rotation of dipoles. Our study sheds light onto a long-standing question on ferroelectric switching in biology and establishes ferroelectricity as an important biophysical property of proteins. This is a critical first step toward resolving its physiological significance and pathological implications.F erroelectricity was first discovered in synthetic materials in 1920 when spontaneous polarization of Rochelle salt was found to be switchable by an external electric field (1). Ferroelectrics thus belongs to a larger class of pyroelectric materials that possess a unique polar axis, which, in turn, belongs to piezoelectrics exhibiting linear coupling between electric and mechanical fields (2). Because of these versatile properties, ferroelectric materials are promising for a wide range of technological applications in data storage, sensing, actuation, energy harvesting, and electro-optic devices (3). Biological tissues, such as bones and tendons, were first observed to be piezoelectric in 1950s (4), and shortly thereafter, pyroelectricity was discovered in a variety of biological materials as well (5, 6). Ever since then, ferroelectricity has been speculated for biological systems, and its potential physiological significance has been suggested (7). For example, it was hypothesized that the conformation transition in voltage-gated ion channels is ferroelectric in nature (8, 9). Nevertheless, indication of ferroelectricity in biological materials has only recently emerged from nanoscale piezoresponse force microscopy (PFM) studies (10-13).This work is motivated by our recent observation of PFM switching in elastin (12), which has generated quite a bit of excitement, although there is still considerable skepticism regarding the notion of biological ferroelectricity. Such reservation is understandable, given the unusual phenomenon of ferroelectric switching in biology, some ambiguities associated with PFM hysteresis, and a current lack of understanding of the basic science underpinning the switching mechanism. Indeed, there is neither macroscopic evidence of ferroelectric switching nor microscopic understan...

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Structure and composition of the elastin fibre in normal and pathological conditions

Cited by 34 publications

References 72 publications

Elastic extracellular matrix of the embryonic chick heart: An immunohistological study using laser confocal microscopy

Elastic extracellular matrix of the embryonic chick heart: An immunohistological study using laser confocal microscopy

The Lysyl Oxidases LOX and LOXL2 Are Necessary and Sufficient to Repress E-cadherin in Hypoxia

Ferroelectric switching of elastin

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