scholarly journals IUGR decreases elastin mRNA expression in the developing rat lung and alters elastin content and lung compliance in the mature rat lung

2011 ◽  
Vol 43 (9) ◽  
pp. 499-505 ◽  
Author(s):  
Lisa A. Joss-Moore ◽  
Yan Wang ◽  
Xing Yu ◽  
Michael S. Campbell ◽  
Christopher W. Callaway ◽  
...  
Keyword(s):  
Elastic Fiber ◽  
Lung Compliance ◽  
Fiber Formation ◽  
Elastic Fibers ◽  
Mrna Levels ◽  
Rat Lung ◽  
Mrna Transcript ◽  
Transcript Levels ◽  
Alveolar Development ◽  
Fiber Deposition

Complications of intrauterine growth restriction (IUGR) include increased pulmonary morbidities and impaired alveolar development. Normal alveolar development depends upon elastin expression and processing, as well as the formation and deposition of elastic fibers. This is true of the human and rat. In this study, we hypothesized that uteroplacental insufficiency (UPI)-induced IUGR decreases mRNA levels of elastin and genes required for elastin fiber synthesis and assembly, at birth (prealveolarization) and postnatal day 7 (midalveolarization) in the rat. We further hypothesized that this would be accompanied by reduced elastic fiber deposition and increased static compliance at postnatal day 21 (mature lung). We used a well characterized rat model of IUGR to test these hypotheses. IUGR decreases mRNA transcript levels of genes essential for elastic fiber formation, including elastin, at birth and day 7. In the day 21 lung, IUGR decreases elastic fiber deposition and increases static lung compliance. We conclude that IUGR decreases mRNA transcript levels of elastic fiber synthesis genes, before and during alveolarization leading to a reduced elastic fiber density and increased static lung compliance in the mature lung. We speculate that the mechanism by which IUGR predisposes to pulmonary disease may be via decreased lung elastic fiber deposition.

scholarly journals Clinical Relevance of Elastin in the Structure and Function of Skin

2021 ◽  
Author(s):  
Leslie Baumann ◽  
Eric F Bernstein ◽  
Anthony S Weiss ◽  
Damien Bates ◽  
Shannon Humphrey ◽  
...  
Keyword(s):  
Wound Healing ◽  
Clinical Relevance ◽  
Structural Integrity ◽  
Elastic Fiber ◽  
Subcutaneous Fat ◽  
Structure And Function ◽  
Fiber Formation ◽  
Elastic Fibers ◽  
Superficial Dermis ◽  
And Function

Abstract Elastin is the main component of elastic fibers, which provide stretch, recoil, and elasticity to the skin. Normal levels of elastic fiber production, organization, and integration with other cutaneous extracellular matrix proteins, proteoglycans, and glycosaminoglycans are integral to maintaining healthy skin structure, function, and youthful appearance. Although elastin has very low turnover, its production decreases after individuals reach maturity and it is susceptible to damage from many factors. With advancing age and exposure to environmental insults, elastic fibers degrade. This degradation contributes to the loss of the skin’s structural integrity; combined with subcutaneous fat loss, this results in looser, sagging skin, causing undesirable changes in appearance. The most dramatic changes occur in chronically sun-exposed skin, which displays sharply altered amounts and arrangements of cutaneous elastic fibers, decreased fine elastic fibers in the superficial dermis connecting to the epidermis, and replacement of the normal collagen-rich superficial dermis with abnormal clumps of solar elastosis material. Disruption of elastic fiber networks also leads to undesirable characteristics in wound healing, and the worsening structure and appearance of scars and stretch marks. Identifying ways to replenish elastin and elastic fibers should improve the skin’s appearance, texture, resiliency, and wound-healing capabilities. However, few therapies are capable of repairing elastic fibers or substantially reorganizing the elastin/microfibril network. This review describes the clinical relevance of elastin in the context of the structure and function of healthy and aging skin, wound healing, and scars and introduces new approaches being developed to target elastin production and elastic fiber formation.

Postnatal alterations in elastic fiber organization precede resistance artery narrowing in SHR

2006 ◽  
Vol 291 (2) ◽  
pp. H804-H812 ◽  
Author(s):  
José M. González ◽  
Ana M. Briones ◽  
Beatriz Somoza ◽  
Craig J. Daly ◽  
Elisabet Vila ◽  
...  
Keyword(s):  
Time Course ◽  
Elastic Fiber ◽  
Elastic Fibers ◽  
Early Event ◽  
Resistance Artery ◽  
Internal Elastic Lamina ◽  
Wall Stiffness ◽  
Fiber Deposition ◽  
Fiber Organization ◽  
Elastic Lamina

Resistance artery narrowing and stiffening are key elements in the pathogenesis of essential hypertension, but their origin is not completely understood. In mesenteric resistance arteries (MRA) from spontaneously hypertensive rats (SHR), we have shown that inward remodeling is associated with abnormal elastic fiber organization, leading to smaller fenestrae in the internal elastic lamina. Our current aim is to determine whether this alteration is an early event that precedes vessel narrowing, or if elastic fiber reorganization in SHR arteries occurs because of the remodeling process itself. Using MRA from 10-day-old, 30-day-old, and 6-mo-old SHR and normotensive Wistar Kyoto rats, we investigated the time course of the development of structural and mechanical alterations (pressure myography), elastic fiber organization (confocal microscopy), and amount of elastin (radioimmunoassay for desmosine) and collagen (picrosirius red). SHR MRA had an impairment of fenestrae enlargement during the first month of life. In 30-day-old SHR, smaller fenestrae and more packed elastic fibers in the internal elastic lamina were paralleled by increased wall stiffness. Collagen and elastin levels were unaltered at this age. MRA from 6-mo-old SHR also had smaller fenestrae and a denser network of adventitial elastic fibers, accompanied by increased collagen content and vessel narrowing. At this age, elastase digestion was less effective in SHR MRA, suggesting a lower susceptibility of elastic fibers to enzymatic degradation. These data suggest that abnormal elastic fiber deposition in SHR increases resistance artery stiffness at an early age, which might participate in vessel narrowing later in life.

Characterization of Cardiac Function and Arterial Mechanics During Early Postnatal Development in Fibulin-5 Null Mice

2013 ◽  
Author(s):  
Victoria Le ◽  
Hiromi Yanagisawa ◽  
Jessica Wagenseil
Keyword(s):  
Matrix Protein ◽  
Elastic Fiber ◽  
Connective Tissue Disorder ◽  
Fiber Formation ◽  
Extracellular Matrix Protein ◽  
Elastic Fibers ◽  
Arterial Mechanics ◽  
Early Postnatal Development ◽  
Complex Process

Fibulin-5 is an extracellular matrix protein that interacts with other proteins during a complex process that results in elastic fiber formation from the elastin precursor, tropoelastin [1]. Elastic fibers are an important component of tissues requiring elasticity, including large arteries, lungs and skin. In mice lacking fibulin-5 ( Fbln5−/−), these tissues contain disorganized elastic fibers and exhibit decreased elasticity [2]. The phenotype of Fbln5−/− mice is similar to that of humans with cutis laxa, a connective tissue disorder characterized by loose skin and narrow arteries with reduced compliance.

Recent updates on the molecular network of elastic fiber formation

2019 ◽  
Vol 63 (3) ◽  
pp. 365-376 ◽  
Author(s):  
Seung Jae Shin ◽  
Hiromi Yanagisawa
Keyword(s):  
Elastic Fiber ◽  
Building Blocks ◽  
Fiber Formation ◽  
Elastic Fibers ◽  
Fiber Network ◽  
Associated Proteins ◽  
Fibrillin 1 ◽  
A Cell ◽  
Self Aggregation

Abstract Elastic fibers confer elasticity and recoiling to tissues and organs and play an essential role in induction of biochemical responses in a cell against mechanical forces derived from the microenvironment. The core component of elastic fibers is elastin (ELN), which is secreted as the monomer tropoelastin from elastogenic cells, and undergoes self-aggregation, cross-linking and deposition on to microfibrils, and assemble into insoluble ELN polymers. For elastic fibers to form, a microfibril scaffold (primarily formed by fibrillin-1 (FBN1)) is required. Numerous elastic fiber-associated proteins are involved in each step of elastogenesis and they instruct and/or facilitate the elastogenesis processes. In this review, we designated five proteins as key molecules in elastic fiber formation, including ELN, FBN1, fibulin-4 (FBLN4), fibulin-5 (FBLN5), and latent TGFβ-binding protein-4 (LTBP4). ELN and FBN1 serve as building blocks for elastic fibers. FBLN5, FBLN4 and LTBP4 have been demonstrated to play crucial roles in elastogenesis through knockout studies in mice. Using these molecules as a platform and expanding the elastic fiber network through the generation of an interactome map, we provide a concise review of elastogenesis with a recent update as well as discuss various biological functions of elastic fiber-associated proteins beyond elastogenesis in vivo.

Developing Elastic Fibers in the Chick Embryo

1968 ◽  
Vol 26 ◽  
pp. 58-59
Author(s):  
C. R. Basom
Keyword(s):  
Electron Microscopy ◽  
Elastic Fiber ◽  
Fiber Formation ◽  
Collagen Fibrils ◽  
Ground Substance ◽  
Elastic Fibers ◽  
The Third ◽  
Immersion Medium ◽  
Individual Unit ◽  
Homogeneous Matrix

The tunica media of the developing chick aorta was examined for elastic fiber formation. Embryos of three to eighteen days incubation age were prepared for electron microscopy by Karnovsky's fixation. Small embryos were fixed by “in toto” immersion: medium sized embryos were previously transected. The aortae of larger embryos were removed prior to fixation. Epon 812 was used for embedment.Irregular masses of amorphous ground substance appeared in the interstitial space of the aortae in three to five day embryos. These masses were located where elastic fibers would later form (Fig. 1). Later loose tangles of microfibrils appeared within the same masses (Fig. 2). In still older embryos, individual unit collagen fibrils appeared within this loose network. At one week's incubation, small elastic fibers could be identified by their homogeneous matrix. These arose within the conglomerate masses described above. At the beginning of the third week compact bundles of colinear unit collagen fibrils appeared (Fig. 3). These fibrils swelled, gradually lost their periodicity and became very lucid (Fig. 4).

scholarly journals Fibulin-2 Is Dispensable for Mouse Development and Elastic Fiber Formation

2007 ◽  
Vol 28 (3) ◽  
pp. 1061-1067 ◽  
Author(s):  
Francois-Xavier Sicot ◽  
Takeshi Tsuda ◽  
Dessislava Markova ◽  
John F. Klement ◽  
Machiko Arita ◽  
...  
Keyword(s):  
Matrix Protein ◽  
Elastic Fiber ◽  
Embryonic Stem ◽  
Fiber Formation ◽  
Extracellular Matrix Protein ◽  
Elastic Fibers ◽  
Mouse Development ◽  
Fibrillin 1

ABSTRACT Fibulin-2 is an extracellular matrix protein belonging to the five-member fibulin family, of which two members have been shown to play essential roles in elastic fiber formation during development. Fibulin-2 interacts with two major constituents of elastic fibers, tropoelastin and fibrillin-1, in vitro and localizes to elastic fibers in many tissues in vivo. The protein is prominently expressed during morphogenesis of the heart and aortic arch vessels and at early stages of cartilage development. To examine its role in vivo, we generated mice that do not express the fibulin-2 gene (Fbln2) through homologous recombination of embryonic stem cells. Unexpectedly, the fibulin-2-null mice were viable and fertile and did not display gross and anatomical abnormalities. Histological and ultrastructural analyses revealed that elastic fibers assembled normally in the absence of fibulin-2. No compensatory up-regulation of mRNAs for other fibulin members was detected in the aorta and skin tissue. However, in the fibulin-2 null aortae, fibulin-1 immunostaining was increased in the inner elastic lamina, where fibulin-2 preferentially localizes. The results demonstrate that fibulin-2 is not required for mouse development and elastic fiber formation and suggest possible functional redundancy between fibulin-1 and fibulin-2.

scholarly journals The role of caveolin-1 in pulmonary matrix remodeling and mechanical properties

2008 ◽  
Vol 295 (6) ◽  
pp. L1007-L1017 ◽  
Author(s):  
O. Le Saux ◽  
K. Teeters ◽  
S. Miyasato ◽  
J. Choi ◽  
G. Nakamatsu ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Signal Transduction ◽  
Airway Resistance ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Elastic Fiber ◽  
Elastic Fibers ◽  
Matrix Remodeling ◽  
Caveolin 1 ◽  
Fiber Deposition

Caveolin-1 (cav1) is a 22-kDa membrane protein essential to the formation of small invaginations in the plasma membrane, called caveolae. The cav1 gene is expressed primarily in adherent cells such as endothelial and smooth muscle cells and fibroblasts. Caveolae contain a variety of signaling receptors, and cav1 notably downregulates transforming growth factor (TGF)-β signal transduction. In pulmonary pathologies such as interstitial fibrosis or emphysema, altered mechanical properties of the lungs are often associated with abnormal ECM deposition. In this study, we examined the physiological functions and the deposition of ECM in cav1−/− mice at various ages (1–12 mo). Cav1−/− mice lack caveolae and by 3 mo of age have significant reduced lung compliance and increased elastance and airway resistance. Pulmonary extravasation of fluid, as part of the cav1−/− mouse phenotype, probably contributed to the alteration of compliance, which was compounded by a progressive increase in deposition of collagen fibrils in airways and parenchyma. We also found that the increased elastance was caused by abundant elastic fiber deposition primarily around airways in cav1−/− mice at least 3 mo old. These observed changes in the ECM composition probably also contribute to the increased airway resistance. The higher deposition of collagen and elastic fibers was associated with increased tropoelastin and col1α2 and col3α1 gene expression in lung tissues, which correlated tightly with increased TGF-β/Smad signal transduction. Our study illustrates that perturbation of cav1 function may contribute to several pulmonary pathologies as the result of the important role played by cav1, as part of the TGF-β signaling pathway, in the regulation of the pulmonary ECM.

Comparison of rat and mouse pulmonary tissue mechanical properties and histology

2002 ◽  
Vol 92 (1) ◽  
pp. 230-234 ◽  
Author(s):  
Débora S. Faffe ◽  
Patricia R. M. Rocco ◽  
Elnara M. Negri ◽  
Walter A. Zin
Keyword(s):  
Mechanical Properties ◽  
Blood Vessel ◽  
Elastic Fiber ◽  
Dynamic Mechanical Properties ◽  
Elastic Fibers ◽  
Rat Lung ◽  
Positive Dependence ◽  
Pulmonary Tissue ◽  
Sinusoidal Oscillations ◽  
The Mean

The present study compares the dynamic mechanical properties and the contents of collagen and elastic fibers (oxytalan + elaunin + fully developed elastic fibers) of mice and rat lung strips. Resistance, elastance (E), and hysteresivity (η) were obtained during sinusoidal oscillations. The relative amounts of blood vessel, bronchial, and alveolar walls, as well as the mean alveolar diameter were determined. In both species, resistance had a negative and E a positive dependence on frequency, whereas η remained unchanged. Mice showed higher E and lower η than rats. Although collagen and elastic fiber contents were similar in both groups, mice had more oxytalan and less elaunin and fully developed elastic fibers than rats. Rats showed less alveolar and more blood vessel walls and higher mean alveolar diameter than mice. In conclusion, mice and rats present distinct tissue mechanical properties, which are accompanied by specific extracellular fiber composition.

scholarly journals Developmental Expression of Latent Transforming Growth Factor β Binding Protein 2 and Its Requirement Early in Mouse Development

2000 ◽  
Vol 20 (13) ◽  
pp. 4879-4887 ◽  
Author(s):  
J. Michael Shipley ◽  
Robert P. Mecham ◽  
Erika Maus ◽  
Jeffrey Bonadio ◽  
Joel Rosenbloom ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Binding Protein ◽  
Elastic Fiber ◽  
Transforming Growth Factor Β ◽  
Fiber Formation ◽  
Developmental Expression ◽  
Elastic Fibers

ABSTRACT Latent transforming growth factor β (TGF-β) binding protein 2 (LTBP-2) is an integral component of elastin-containing microfibrils. We studied the expression of LTBP-2 in the developing mouse and rat by in situ hybridization, using tropoelastin expression as a marker of tissues participating in elastic fiber formation. LTBP-2 colocalized with tropoelastin within the perichondrium, lung, dermis, large arterial vessels, epicardium, pericardium, and heart valves at various stages of rodent embryonic development. Both LTBP-2 and tropoelastin expression were seen throughout the lung parenchyma and within the cortex of the spleen in the young adult mouse. In the testes, LTBP-2 expression was seen within lumenal cells of the epididymis in the absence of tropoelastin. Collectively, these results imply that LTBP-2 plays a structural role within elastic fibers in most cases. To investigate its importance in development, mice with a targeted disruption of the Ltbp2 gene were generated.Ltbp2 −/− mice die between embryonic day 3.5 (E3.5) and E6.5. LTBP-2 expression was not detected by in situ hybridization in E6.5 embryos but was detected in E3.5 blastocysts by reverse transcription-PCR. These results are not consistent with the phenotypes of TGF-β knockout mice or mice with knockouts of other elastic fiber proteins, implying that LTBP-2 performs a yet undiscovered function in early development, perhaps in implantation.

scholarly journals Elastic Laminar Reorganization Occurs with Outward Diameter Expansion during Collateral Artery Growth and Requires Lysyl Oxidase for Stabilization

2021 ◽  
Author(s):  
Ryan M McEnaney ◽  
Dylan D McCreary ◽  
Nolan Skirtich ◽  
Elizabeth Andraska ◽  
Ulka Sachdev ◽  
...  
Keyword(s):  
Structural Changes ◽  
Lysyl Oxidase ◽  
Elastic Fiber ◽  
Multiphoton Microscopy ◽  
Fiber Formation ◽  
Elastic Fibers ◽  
Large Artery ◽  
Luminal Diameter ◽  
Collateral Arteries ◽  
Collateral Artery

When a large artery becomes occluded, hemodynamic changes stimulate remodeling of arterial networks to form collateral arteries in a process termed arteriogenesis. However, the structural changes necessary for collateral remodeling have not been defined. We hypothesize that decon-struction of the extracellular matrix is essential to the remodeling of smaller arteries into effective collaterals. Using multiphoton microscopy, we analyzed collagen and elastin structure in maturing collateral arteries isolated from ischemic rat hindlimbs. Collateral arteries harvested at different timepoints showed progressive diameter expansion associated with striking rearrangement of in-ternal elastic lamina (IEL) into a loose fibrous mesh, a pattern persisting at 8 weeks. Despite a 2.5-fold increase in luminal diameter, total elastin content remained unchanged in collaterals compared with control arteries. Among the collateral midzones, baseline elastic fiber content is low. Outward remodeling of these vessels with a 10-20 fold diameter increase was associated with fractures of the elastic fibers and evidence of increased wall tension as demonstrated by straight-ening of the adventitial collagen. Inhibition of lysyl oxidase (LOX) function with β-aminopropionitrile resulted in severe fragmentation or complete loss of continuity of the IEL in developing collaterals. Collateral artery development is associated with permanent redistribution of existing elastic fibers to accommodate diameter growth. We found no evidence of new elastic fiber formation. Stabilization of the arterial wall during outward remodeling is necessary and dependent on LOX activity.

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