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.

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.

scholarly journals Human Microfibrillar-Associated Protein 4 (MFAP4) Gene Promoter: A TATA-Less Promoter That Is Regulated by Retinol and Coenzyme Q10 in Human Fibroblast Cells

2020 ◽  
Vol 21 (21) ◽  
pp. 8392
Author(s):  
Ying-Ju Lin ◽  
An-Ni Chen ◽  
Xi Jiang Yin ◽  
Chunxiang Li ◽  
Chih-Chien Lin
Keyword(s):  
Coenzyme Q10 ◽  
Elastic Fiber ◽  
Gene Promoter ◽  
Fiber Formation ◽  
Elastic Fibers ◽  
Structural Components ◽  
Connective Tissues ◽  
Human Fibroblast Cells ◽  
Fibrillin 1 ◽  
Species Specific

Elastic fibers are one of the major structural components of the extracellular matrix (ECM) in human connective tissues. Among these fibers, microfibrillar-associated protein 4 (MFAP4) is one of the most important microfibril-associated glycoproteins. MFAP4 has been found to bind with elastin microfibrils and interact directly with fibrillin-1, and then aid in elastic fiber formation. However, the regulations of the human MFAP4 gene are not so clear. Therefore, in this study, we firstly aimed to analyze and identify the promoter region of the human MFAP4 gene. The results indicate that the human MFAP4 promoter is a TATA-less promoter with tissue- and species-specific properties. Moreover, the promoter can be up-regulated by retinol and coenzyme Q10 (coQ10) in Detroit 551 cells.

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.

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 Elastic Fibers and Large Artery Mechanics in Animal Models of Development and Disease

2018 ◽  
Vol 140 (2) ◽  
Author(s):  
Maria Gabriela Espinosa ◽  
Marius Catalin Staiculescu ◽  
Jungsil Kim ◽  
Eric Marin ◽  
Jessica E. Wagenseil
Keyword(s):  
Animal Models ◽  
Mechanical Behavior ◽  
Computational Models ◽  
Mechanical Response ◽  
Elastic Fiber ◽  
High Stress ◽  
Elastic Fibers ◽  
Large Artery ◽  
Fiber Network ◽  
Pulsatile Pressure

Development of a closed circulatory system requires that large arteries adapt to the mechanical demands of high, pulsatile pressure. Elastin and collagen uniquely address these design criteria in the low and high stress regimes, resulting in a nonlinear mechanical response. Elastin is the core component of elastic fibers, which provide the artery wall with energy storage and recoil. The integrity of the elastic fiber network is affected by component insufficiency or disorganization, leading to an array of vascular pathologies and compromised mechanical behavior. In this review, we discuss how elastic fibers are formed and how they adapt in development and disease. We discuss elastic fiber contributions to arterial mechanical behavior and remodeling. We primarily present data from mouse models with elastic fiber deficiencies, but suggest that alternate small animal models may have unique experimental advantages and the potential to provide new insights. Advanced ultrastructural and biomechanical data are constantly being used to update computational models of arterial mechanics. We discuss the progression from early phenomenological models to microstructurally motivated strain energy functions for both collagen and elastic fiber networks. Although many current models individually account for arterial adaptation, complex geometries, and fluid–solid interactions (FSIs), future models will need to include an even greater number of factors and interactions in the complex system. Among these factors, we identify the need to revisit the role of time dependence and axial growth and remodeling in large artery mechanics, especially in cardiovascular diseases that affect the mechanical integrity of the elastic fibers.

scholarly journals Lung matrix and vascular remodeling in mechanically ventilated elastin haploinsufficient newborn mice

2015 ◽  
Vol 308 (5) ◽  
pp. L464-L478 ◽  
Author(s):  
Anne Hilgendorff ◽  
Kakoli Parai ◽  
Robert Ertsey ◽  
Edwin Navarro ◽  
Noopur Jain ◽  
...  
Keyword(s):  
Lysyl Oxidase ◽  
Elastic Fiber ◽  
Growth Arrest ◽  
Subsequent Development ◽  
Fiber Formation ◽  
Lung Growth ◽  
Elastase Activity ◽  
Newborn Mice ◽  
Fibrillin 1 ◽  
Lung Capillaries

Elastin plays a pivotal role in lung development. We therefore queried if elastin haploinsufficient newborn mice ( Eln+/−) would exhibit abnormal lung structure and function related to modified extracellular matrix (ECM) composition. Because mechanical ventilation (MV) has been linked to dysregulated elastic fiber formation in the newborn lung, we also asked if elastin haploinsufficiency would accentuate lung growth arrest seen after prolonged MV of neonatal mice. We studied 5-day-old wild-type ( Eln+/+) and Eln+/− littermates at baseline and after MV with air for 8–24 h. Lungs of unventilated Eln+/− mice contained ∼50% less elastin and ∼100% more collagen-1 and lysyl oxidase compared with Eln+/+ pups. Eln+/− lungs contained fewer capillaries than Eln+/+ lungs, without discernible differences in alveolar structure. In response to MV, lung tropoelastin and elastase activity increased in Eln+/+ neonates, whereas tropoelastin decreased and elastase activity was unchanged in Eln+/− mice. Fibrillin-1 protein increased in lungs of both groups during MV, more in Eln+/− than in Eln+/+ pups. In both groups, MV caused capillary loss, with larger and fewer alveoli compared with unventilated controls. Respiratory system elastance, which was less in unventilated Eln+/− compared with Eln+/+ mice, was similar in both groups after MV. These results suggest that elastin haploinsufficiency adversely impacts pulmonary angiogenesis and that MV dysregulates elastic fiber integrity, with further loss of lung capillaries, lung growth arrest, and impaired respiratory function in both Eln+/+ and Eln+/− mice. Paucity of lung capillaries in Eln+/− newborns might help explain subsequent development of pulmonary hypertension previously reported in adult Eln+/− mice.

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.

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 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.

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