scholarly journals Neuraminidase-1 is required for the normal assembly of elastic fibers

2008 ◽  
Vol 295 (4) ◽  
pp. L637-L647 ◽  
Author(s):  
Barry Starcher ◽  
Alessandra d'Azzo ◽  
Patrick W. Keller ◽  
Gottipati K. Rao ◽  
Deepa Nadarajah ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Smooth Muscle ◽  
Random Distribution ◽  
Elastic Fiber ◽  
Abnormal Development ◽  
Elastic Fibers ◽  
Tight Skin ◽  
Fibrillin 1 ◽  
Histopathological Effects

The assembly of elastic fibers in tissues that undergo repeated cycles of extension and recoil, such as the lungs and blood vessels, is dependent on the proper interaction and alignment of tropoelastin with a microfibrillar scaffold. Here, we describe in vivo histopathological effects of neuraminidase-1 (Neu1) deficiency on elastin assembly in the lungs and aorta of mice. These mice exhibited a tight-skin phenotype very similar to the Tsk mouse. Normal septation of Neu1-null mice did not occur in neonatal mice, resulting in enlarged alveoli that were maintained in adults. The abnormal development of elastic fibers was remarkable under electron microscopy and confirmed by the overlapping distribution of elastin, fibrillin-1, fibrillin-2, and fibulin-5 (Fib-5) by the light microscopy immunostainings. Fib-5 fibers appeared diffuse and unorganized around the alveolar walls and the apex of developing secondary septal crests. Fibrillin-2 deposition was also abnormal in neonatal and adult lungs. Dispersion of myofibroblasts appeared abnormal in developing lungs of Neu1-null mice, with a random distribution of myofibroblast around the alveolar walls, rather than concentrating at sites of elastin synthesis. The elastic lamellae in the aorta of the Neu1-null mice were thinner and separated by hypertrophic smooth muscle cells that were surrounded by an excess of the sialic acid-containing moieties. The concentration of elastin, as measure by desmosine levels, was significantly reduced in the aorta of Neu1-null mice. Message levels for tropoelastin and Fib-5 were normal, suggesting the elastic fiber defects in Neu1-null mice result from impaired extracellular assembly.

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.

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.

Abstract 424: Vascular Smooth Muscle Cell Expression of S100a12 in Vivo Induces Enhanced Oxidative Stress & Vascular Remodeling

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Marion Hofmann Bowman ◽  
Jeannine Wilk ◽  
Gene Kim ◽  
Yanmin Zhang ◽  
Jalees Rehman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Smooth Muscle ◽  
Vascular Remodeling ◽  
Oxidative Dna Damage ◽  
Fold Increase ◽  
Brdu Incorporation ◽  
Elastic Fibers ◽  
Nuclear Staining

S100A12 is a small calcium binding protein that is a signal transduction ligand of the receptor for advance glycation endproducts (RAGE). S100A12, like RAGE, is expressed in the vessel wall of atherosclerotic vasculature, particularly in smooth muscle cells (SMC). While RAGE has been extensively implicated in inflammatory states such as atherosclerosis, the role of S100A12 is less clear. We tested the hypothesis that expression of human S100A12 directly exacerbates vascular inflammation. Several lines of Bl6/J transgenic mice (tg) expressing human S100A12 in SMC under control of the SM22a promoter were generated. Primary aortic SMC from tg and wild type (wt) littermates were isolated and analyzed for (i) proliferation using MTS/Formazan Assay and BrdU incorporation, (ii) oxidative stress using using flow cytometry with MitoSOX antibody, oxidative DNA damage using immunofluorescence microscopy with anti-8-oxo-dG antibody, and NF-kB activation measured by EMSA and (iii) cytokine expression measured by IL-6 ELISA. Furthermore, the aortas from tg and wt mice were examined. Results: Tg but not wt SMC expressed S100A12 protein. Tg SMC had a significant 1.9 to 2.7 fold increase in conversion of MTS into Formazan at 24–96 hours likely reflective of increased metabolic activity since BrdU incorporation into DNA was less in tg compared to wt SMC (4% vs 21% positive BrdU nuclei, p <0.05). Tg SMC showed significantly higher levels of mitochondrial generated ROS, nuclear staining for oxidative DNA damage which was not detected in the nuclei of wt SMC’s, and a 2.5 fold increase in NFkB activity. IL-6 production at baseline was higher in tg SMC’s (615 vs 213 pg/ml, p< 0.05) and increased dramatically after LPS treatment (10 ng/ml) in tg SMC’s (2130 vs 415 pg/ml). Histologic examination of the thoracic aorta at 10 weeks of age revealed increased collagen deposition in the aortic media with fragmentation and disarray of elastic fibers. In vivo ultrasound revealed a progressive dilation of the aortic arch from age 10 weeks to 16 weeks of age (1.27 to 1.60 mm, p<0.05) in tg but not in wt littermate mice (1.30 to 1.33 mm, p=0.1). These data reveal the novel finding that targeted expression of human S100A12 in SMC modulates oxidative stress, inflammation and vascular remodeling.

Elastin exhibits a distinctive temporal and spatial pattern of distribution in the developing chick limb in association with the establishment of the cartilaginous skeleton

1994 ◽  
Vol 107 (9) ◽  
pp. 2623-2634 ◽  
Author(s):  
J.M. Hurle ◽  
G. Corson ◽  
K. Daniels ◽  
R.S. Reiter ◽  
L.Y. Sakai ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Spatial Pattern ◽  
Elastic Fiber ◽  
Spatial Location ◽  
Limb Bud ◽  
Confocal Laser ◽  
Elastic Fibers ◽  
Type I ◽  
Temporal And Spatial

In this work we have analyzed the presence of elastic components in the extracellular matrices of the developing chick leg bud. The distributions of elastin and fibrillin were studied immunohistochemically in whole-mount preparations using confocal laser microscopy. The association of these constituents of the elastic matrix with other components of the extracellular matrix was also studied, using several additional antibodies. Our results reveal the transient presence of an elastin-rich scaffold of extracellular matrix fibrillar material in association with the establishment of the cartilaginous skeleton of the leg bud. The scaffold consisted of elastin-positive fibers extending from the ectodermal surface of the limb to the central cartilage-forming regions and between adjacent cartilages. Fibrillin immunolabeling was negative in this fibrillar scaffold while other components of the extracellular matrix including: tenascin, laminin and collagens type I, type III and type VI; appeared codistributed with elastin in some regions of the scaffold. Progressive changes in the spatial pattern of distribution of the elastin-positive scaffold were detected in explant cultures in which one expects a modification in the mechanical stresses of the tissues related to growth. A scaffold of elastin comparable to that found in vivo was also observed in high-density micromass cultures of isolated limb mesodermal cells. In this case the elastic fibers are observed filling the spaces located between the cartilaginous nodules. The fibers become reoriented and attach to the ectodermal basal surface when an ectodermal fragment is located at the top of the growing micromass. Our results suggest that the formation of the cartilaginous skeleton of the limb involves the segregation of the undifferentiated limb mesenchyme into chondrogenic and elastogenic cell lineages. Further, a role for the elastic fiber scaffold in coordinating the size and the spatial location of the cartilaginous skeletal elements within the limb bud is also suggested from our observations.

scholarly journals Effects of chronic l-NAME treatment lung tissue mechanics, eosinophilic and extracellular matrix responses induced by chronic pulmonary inflammation

2008 ◽  
Vol 294 (6) ◽  
pp. L1197-L1205 ◽  
Author(s):  
Patrícia Angeli ◽  
Carla M. Prado ◽  
Débora G. Xisto ◽  
Pedro L. Silva ◽  
Caroline P. Pássaro ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Lung Tissue ◽  
Pulmonary Inflammation ◽  
Elastic Fiber ◽  
Tissue Mechanics ◽  
Elastic Fibers ◽  
Distal Lung ◽  
Alveolar Septa

The importance of lung tissue in asthma pathophysiology has been recently recognized. Although nitric oxide mediates smooth muscle tonus control in airways, its effects on lung tissue responsiveness have not been investigated previously. We hypothesized that chronic nitric oxide synthase (NOS) inhibition by Nω-nitro-l-arginine methyl ester (l-NAME) may modulate lung tissue mechanics and eosinophil and extracellular matrix remodeling in guinea pigs with chronic pulmonary inflammation. Animals were submitted to seven saline or ovalbumin exposures with increasing doses (1∼5 mg/ml for 4 wk) and treated or not with l-NAME in drinking water. After the seventh inhalation (72 h), animals were anesthetized and exsanguinated, and oscillatory mechanics of lung tissue strips were performed in baseline condition and after ovalbumin challenge (0.1%). Using morphometry, we assessed the density of eosinophils, neuronal NOS (nNOS)- and inducible NOS (iNOS)-positive distal lung cells, smooth muscle cells, as well as collagen and elastic fibers in lung tissue. Ovalbumin-exposed animals had an increase in baseline and maximal tissue resistance and elastance, eosinophil density, nNOS- and iNOS-positive cells, the amount of collagen and elastic fibers, and isoprostane-8-PGF2α expression in the alveolar septa compared with controls ( P < 0.05). l-NAME treatment in ovalbumin-exposed animals attenuated lung tissue mechanical responses ( P < 0.01), nNOS- and iNOS-positive cells, elastic fiber content ( P < 0.001), and isoprostane-8-PGF2α in the alveolar septa ( P < 0.001). However, this treatment did not affect the total number of eosinophils and collagen deposition. These data suggest that NO contributes to distal lung parenchyma constriction and to elastic fiber deposition in this model. One possibility may be related to the effects of NO activating the oxidative stress pathway.

scholarly journals FINE STRUCTURE OF SMOOTH MUSCLE CELLS GROWN IN TISSUE CULTURE

1971 ◽  
Vol 49 (1) ◽  
pp. 21-34 ◽  
Author(s):  
Gordon R. Campbell ◽  
Yasuo Uehara ◽  
Gerda Mark ◽  
Geoffrey Burnstock
Keyword(s):  
Electron Microscopy ◽  
Smooth Muscle ◽  
Fine Structure ◽  
Cell Membrane ◽  
Smooth Muscle Cells ◽  
Phase Contrast ◽  
Muscle Cells ◽  
Different Types ◽  
Membrane Infoldings

The fine structure of smooth muscle cells of the embryo chicken gizzard cultured in monolayer was studied by phase-contrast optics and electron microscopy. The smooth muscle cells were irregular in shape, but tended to be elongate. The nucleus usually contained prominent nucleoli and was large in relation to the cell body. When fixed with glutaraldehyde, three different types of filaments were noted in the cytoplasm: thick (150–250 A in diameter) and thin (30–80 A in diameter) myofilaments, many of which were arranged in small bundles throughout the cytoplasm and which were usually associated with dark bodies; and filaments with a diameter of 80–110 A which were randomly orientated and are not regarded as myofilaments. Some of the aggregated ribosomes were helically arranged. Mitochondria, Golgi apparatus, and dilated rough endoplasmic reticulum were prominent. In contrast to in vivo muscle cells, micropinocytotic vesicles along the cell membrane were rare and dense areas were usually confined to cell membrane infoldings. These cells are compared to in vivo embryonic smooth muscle and adult muscle after treatment with estrogen. Monolayers of cultured smooth muscle will be of particular value in relating ultrastructural features to functional observations on the same cells.

scholarly journals Developmental expression of fibrillin genes suggests heterogeneity of extracellular microfibrils.

1995 ◽  
Vol 129 (4) ◽  
pp. 1165-1176 ◽  
Author(s):  
H Zhang ◽  
W Hu ◽  
F Ramirez
Keyword(s):  
Spatial Organization ◽  
Developmental Stages ◽  
Elastic Fiber ◽  
Biomechanical Properties ◽  
Developmental Expression ◽  
Elastic Fibers ◽  
Fiber Assembly ◽  
Structural Support ◽  
Functional Relationships ◽  
Fibrillin 1

Extracellular microfibrils, alone or in association with elastin, confer critical biomechanical properties on a variety of connective tissues. Little is known about the composition of the microfibrils or the factors responsible for their spatial organization into tissue-specific macroaggregates. Recent work has revealed the existence of two structurally related microfibrillar components, termed fibrillin-1 and fibrillin-2. The functional relationships between these glycoproteins and between them and other components of the microfibrils and elastic fibers are obscure. As a first step toward elucidating these important points, we compared the expression pattern of the fibrillin genes during mammalian embryogenesis. The results revealed that the two genes are differentially expressed, in terms of both developmental stages and tissue distribution. In the majority of cases, fibrillin-2 transcripts appear earlier and accumulate for a shorter period of time than fibrillin-1 transcripts. Synthesis of fibrillin-1 correlates with late morphogenesis and the appearance of well-defined organ structures; fibrillin-2 synthesis, on the other hand, coincides with early morphogenesis and, in particular, with the beginning of elastogenesis. The findings lend indirect support to our original hypothesis stating that fibrillins contribute to the compositional and functional heterogeneity of the microfibrils. The available evidence is also consistent with the notion that the fibrillins might have distinct, but related roles in microfibril physiology. Accordingly, we propose that fibrillin-1 provides mostly force-bearing structural support, whereas fibrillin-2 predominantly regulates the early process of elastic fiber assembly.

scholarly journals Stereological study of the elastic fiber and smooth muscle cell system in the bovine and buffalo penis

2013 ◽  
Vol 33 (suppl 1) ◽  
pp. 107-112 ◽  
Author(s):  
Ilma C.A. Ribeiro ◽  
Marcelo Abidu-Figueiredo ◽  
Fabíola B. Costa ◽  
Marco A. Pereira-Sampaio ◽  
Maurício A. Chagas
Keyword(s):  
Smooth Muscle ◽  
Elastic System ◽  
Tunica Albuginea ◽  
Elastic Fiber ◽  
Corpus Cavernosum ◽  
Volume Density ◽  
Cell System ◽  
Elastic Fibers ◽  
Corpus Spongiosum ◽  
Significant Difference

Samples of ten penises of Mediterranean buffaloes and ten penises of Red Sindhi cattle were used. The thickness of the tunica albuginea (TA), distribution of smooth muscle cells (SMC) and volume density (Vv) of elastic system fibers in TA, corpus cavernosum (CC) and corpus spongiosum (CS) were evaluated. The Vv of elastic system fibers in buffalo and bovine penis was respectively 4.07% ±0.88% and 3.36% ±1.21% in TA; 17.32% ±2.21% and 13.14% ±1.27% (CC), 26.58% ±4.31% and 31.36% ±3.67% (CS). The CC of buffalo presented higher Vv of elastic fibers than bovine, while in the CS the Vv of elastic fibers in buffaloes was smaller than in cattle. The TA thickness showed a significant difference among the species studied. The arrangement of SMC in the bovine penises and in the water buffalo suggests that this pattern is common to animals that have fibroelastic penises.

scholarly journals Progressive Microstructural Deterioration Dictates Evolving Biomechanical Dysfunction in the Marfan Aorta

2021 ◽  
Vol 8 ◽  
Author(s):  
Cristina Cavinato ◽  
Minghao Chen ◽  
Dar Weiss ◽  
Maria Jesús Ruiz-Rodríguez ◽  
Martin A. Schwartz ◽  
...  
Keyword(s):  
Structural Integrity ◽  
Ex Vivo ◽  
Elastic Fiber ◽  
Three Dimensional ◽  
Microstructural Characterization ◽  
Aortic Aneurysms ◽  
Elastic Fibers ◽  
Cell Phenotype ◽  
Medial Degeneration ◽  
Fibrillin 1

Medial deterioration leading to thoracic aortic aneurysms arises from multiple causes, chief among them mutations to the gene that encodes fibrillin-1 and leads to Marfan syndrome. Fibrillin-1 microfibrils associate with elastin to form elastic fibers, which are essential structural, functional, and instructional components of the normal aortic wall. Compromised elastic fibers adversely impact overall structural integrity and alter smooth muscle cell phenotype. Despite significant progress in characterizing clinical, histopathological, and mechanical aspects of fibrillin-1 related aortopathies, a direct correlation between the progression of microstructural defects and the associated mechanical properties that dictate aortic functionality remains wanting. In this paper, age-matched wild-type, Fbn1C1041G/+, and Fbn1mgR/mgR mouse models were selected to represent three stages of increasing severity of the Marfan aortic phenotype. Ex vivo multiphoton imaging and biaxial mechanical testing of the ascending and descending thoracic aorta under physiological loading conditions demonstrated that elastic fiber defects, collagen fiber remodeling, and cell reorganization increase with increasing dilatation. Three-dimensional microstructural characterization further revealed radial patterns of medial degeneration that become more uniform with increasing dilatation while correlating strongly with increased circumferential material stiffness and decreased elastic energy storage, both of which comprise aortic functionality.

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).

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