Hyperoxic exposure of developing rat lung decreases tropoelastin mRNA levels that rebound postexposure

1993 ◽  
Vol 265 (3) ◽  
pp. L293-L300 ◽  
Author(s):  
M. C. Bruce ◽  
E. N. Bruce ◽  
K. Janiga ◽  
A. Chetty
Keyword(s):  
Elastic Fiber ◽  
Lung Parenchyma ◽  
Regulatory Control ◽  
Separate Experiment ◽  
Elastic Fibers ◽  
Mrna Levels ◽  
Fiber Assembly ◽  
Total Length ◽  
Rat Pups ◽  
Hyperoxic Exposure

These studies were undertaken to determine whether tropoelastin message expression in lung parenchymal tissue is altered in rats reared in an hyperoxic environment during the period of time that alveolar septation normally occurs. Rat pups were exposed to > 95% oxygen from days 4 to 14 and killed during the exposure and recovery periods. Results of in situ hybridizations indicated a delay in peak tropoelastin (TE) message levels in oxygen-exposed rats vs. controls, day 16 vs. day 11, respectively. In addition, lung parenchymal TE mRNA levels in the oxygen-exposed pups remained elevated through day 23, 1 wk after TE mRNA levels had decreased in controls. These observations suggest that the regulatory control of elastin synthesis during lung alveolar septation is altered by hyperoxic exposure. In a separate experiment, rat pups were exposed to > 95% oxygen during the period of alveolarization and followed for 4 wk postexposure. Pulmonary function measurements were conducted to determine whether lung function was altered postexposure and, if so, whether recovery occurred. We also used stereological techniques to quantitate the total length of lung parenchymal elastic fibers to determine whether elastic fiber content in the oxygen-exposed pups was restored to normal levels during the month postexposure. Although the total length of elastic fibers in lung parenchyma was found to be greater in oxygen-exposed than control pups from postnatal days 22 to 41, pressure-volume curves indicated that lungs of the oxygen-exposed pups tended to be more compliant than controls, suggesting that abnormal elastic fiber assembly might have been a contributing factor.

scholarly journals Enhancement of elastin expression by transdermal administration of sialidase isozyme Neu2

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Akira Minami ◽  
Yuka Fujita ◽  
Jun Goto ◽  
Ayano Iuchi ◽  
Kosei Fujita ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Skin Diseases ◽  
Lower Layer ◽  
Elastic Fiber ◽  
Sialic Acid Residue ◽  
Elastic Fibers ◽  
Transdermal Administration ◽  
Sialidase Activity ◽  
Fiber Assembly ◽  
Senescence Accelerated Mice

AbstractReduction of elastin in the skin causes various skin diseases as well as wrinkles and sagging with aging. Sialidase is a hydrolase that cleaves a sialic acid residue from sialoglycoconjugate. Cleavage of sialic acid from microfibrils by the sialidase isozyme Neu1 facilitates elastic fiber assembly. In the present study, we showed that a lower layer of the dermis and muscle showed relatively intense sialidase activity. The sialidase activity in the skin decreased with aging. Choline and geranate (CAGE), one of the ionic liquids, can deliver the sialidase subcutaneously while maintaining the enzymatic activity. The elastin level in the dermis was increased by applying sialidase from Arthrobacter ureafaciens (AUSA) with CAGE on the skin for 5 days in rats and senescence-accelerated mice prone 1 and 8. Sialidase activity in the dermis was considered to be mainly due to Neu2 based on the expression level of sialidase isozyme mRNA. Transdermal administration of Neu2 with CAGE also increased the level of elastin in the dermis. Therefore, not only Neu1 but also Neu2 would be involved in elastic fiber assembly. Transdermal administration of sialidase is expected to be useful for improvement of wrinkles and skin disorders due to the loss of elastic fibers.

scholarly journals Effect of hyperoxic exposure during early development on neurotrophin expression in the carotid body and nucleus tractus solitarii

2012 ◽  
Vol 112 (10) ◽  
pp. 1762-1772 ◽  
Author(s):  
Raul Chavez-Valdez ◽  
Ariel Mason ◽  
Ana R. Nunes ◽  
Frances J. Northington ◽  
Clarke Tankersley ◽  
...  
Keyword(s):  
Protein Expression ◽  
Carotid Body ◽  
Acute Hypoxia ◽  
Synaptic Activity ◽  
Nucleus Tractus Solitarii ◽  
Mrna Levels ◽  
Bdnf Mrna ◽  
Rat Pups ◽  
Hyperoxic Exposure ◽  
And Shifts

Synaptic activity can modify expression of neurotrophins, which influence the development of neuronal circuits. In the newborn rat, early hyperoxia silences the synaptic activity and input from the carotid body, impairing the development and function of chemoreceptors. The purpose of this study was to determine whether early hyperoxic exposure, sufficient to induce hypoplasia of the carotid body and decrease the number of chemoafferents, would also modify neurotrophin expression within the nucleus tractus solitarii (nTS). Rat pups were exposed to hyperoxia (fraction of inspired oxygen 0.60) or normoxia until 7 or 14 days of postnatal development (PND). In the carotid body, hyperoxia decreased brain-derived neurotrophic factor (BDNF) protein expression by 93% ( P = 0.04) after a 7-day exposure, followed by a decrease in retrogradely labeled chemoafferents by 55% ( P = 0.004) within the petrosal ganglion at 14 days. Return to normoxia for 1 wk after a 14-day hyperoxic exposure did not reverse this effect. In the nTS, hyperoxia for 7 days: 1) decreased BDNF gene expression by 67% and protein expression by 18%; 2) attenuated upregulation of BDNF mRNA levels in response to acute hypoxia; and 3) upregulated p75 neurotrophic receptor, truncated tropomyosin kinase B (inactive receptor), and cleaved caspase-3. These effects were not observed in the locus coeruleus (LC). Hyperoxia for 14 days also decreased tyrosine hydroxylase levels by 18% ( P = 0.04) in nTS but not in the LC. In conclusion, hyperoxic exposure during early PND reduces neurotrophin levels in the carotid body and the nTS and shifts the balance of neurotrophic support from prosurvival to proapoptotic in the nTS, the primary brain stem site for central integration of sensory and autonomic inputs.

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 Effect of vaginal distention on elastic fiber synthesis and matrix degradation in the vaginal wall: potential role in the pathogenesis of pelvic organ prolapse

2008 ◽  
Vol 295 (4) ◽  
pp. R1351-R1358 ◽  
Author(s):  
D. D. Rahn ◽  
J. F. Acevedo ◽  
R. A. Word
Keyword(s):  
Pelvic Organ Prolapse ◽  
Protease Activity ◽  
Potential Role ◽  
Elastic Fiber ◽  
Pelvic Organ ◽  
Vaginal Wall ◽  
Elastic Fibers ◽  
Wild Type ◽  
Fiber Assembly ◽  
Pregnant Mice

Matrix metalloprotease (MMP) activity is increased in the postpartum vagina of wild-type (WT) animals. This degradative activity is also accompanied by a burst in elastic fiber synthesis and assembly. The mechanisms that precipitate these changes are unclear. The goals of this study were to determine how vaginal distention (such as in parturition) affects elastic fiber homeostasis in the vaginal wall and the potential significance of these changes in the pathogenesis of pelvic organ prolapse. Vaginal distention with a balloon simulating parturition resulted in increased MMP-2 and MMP-9 activity in the vaginal wall of nonpregnant and pregnant animals. This was accompanied by visible fragmented and disrupted elastic fibers in the vaginal wall. In nonpregnant animals, the abundant amounts of tropoelastin and fibulin-5 in the vagina were not increased further by distention. In contrast, in pregnant animals, the suppressed levels of both proteins were increased 3-fold after vaginal distention. Distention performed in fibulin-5-deficient ( Fbln5−/−) mice with defective elastic fiber synthesis and assembly induced accelerated pelvic organ prolapse, which never recovered. We conclude that, in pregnant mice, vaginal distention results in increased protease activity in the vaginal wall but also increased synthesis of proteins important for elastic fiber assembly. Distention may thereby contribute to the burst of elastic fiber synthesis in the postpartum vagina. The finding that distention results in accelerated pelvic organ prolapse in Fbln5−/− animals, but not in WT, indicates that elastic fiber synthesis is crucial for recovery of the vaginal wall from distention-induced increases in vaginal protease activity.

scholarly journals Elastin, arterial mechanics, and cardiovascular disease

2018 ◽  
Vol 315 (2) ◽  
pp. H189-H205 ◽  
Author(s):  
Austin J. Cocciolone ◽  
Jie Z. Hawes ◽  
Marius C. Staiculescu ◽  
Elizabeth O. Johnson ◽  
Monzur Murshed ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Aortic Stenosis ◽  
Autosomal Dominant ◽  
Elastic Fiber ◽  
Cutis Laxa ◽  
Supravalvular Aortic Stenosis ◽  
Elastic Fibers ◽  
Arterial Mechanics ◽  
Fiber Assembly

Large, elastic arteries are composed of cells and a specialized extracellular matrix that provides reversible elasticity and strength. Elastin is the matrix protein responsible for this reversible elasticity that reduces the workload on the heart and dampens pulsatile flow in distal arteries. Here, we summarize the elastin protein biochemistry, self-association behavior, cross-linking process, and multistep elastic fiber assembly that provide large arteries with their unique mechanical properties. We present measures of passive arterial mechanics that depend on elastic fiber amounts and integrity such as the Windkessel effect, structural and material stiffness, and energy storage. We discuss supravalvular aortic stenosis and autosomal dominant cutis laxa-1, which are genetic disorders caused by mutations in the elastin gene. We present mouse models of supravalvular aortic stenosis, autosomal dominant cutis laxa-1, and graded elastin amounts that have been invaluable for understanding the role of elastin in arterial mechanics and cardiovascular disease. We summarize acquired diseases associated with elastic fiber defects, including hypertension and arterial stiffness, diabetes, obesity, atherosclerosis, calcification, and aneurysms and dissections. We mention animal models that have helped delineate the role of elastic fiber defects in these acquired diseases. We briefly summarize challenges and recent advances in generating functional elastic fibers in tissue-engineered arteries. We conclude with suggestions for future research and opportunities for therapeutic intervention in genetic and acquired elastinopathies.

scholarly journals Analysis of dermal elastic fibers in the absence of fibulin-5 reveals potential roles for fibulin-5 in elastic fiber assembly

2009 ◽  
Vol 28 (4) ◽  
pp. 211-220 ◽  
Author(s):  
Jiwon Choi ◽  
Andreas Bergdahl ◽  
Qian Zheng ◽  
Barry Starcher ◽  
Hiromi Yanagisawa ◽  
...  
Keyword(s):  
Elastic Fiber ◽  
Elastic Fibers ◽  
Fiber Assembly

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 Characterization of spontaneous air space enlargement in mice lacking microfibrillar-associated protein 4

2015 ◽  
Vol 308 (11) ◽  
pp. L1114-L1124 ◽  
Author(s):  
Anne Trommelholt Holm ◽  
Helle Wulf-Johansson ◽  
Svend Hvidsten ◽  
Patricia Troest Jorgensen ◽  
Anders Schlosser ◽  
...  
Keyword(s):  
Elastic Fiber ◽  
Lung Parenchyma ◽  
Elastic Fibers ◽  
Breath Hold ◽  
Transmission Electron ◽  
Air Space ◽  
Alveolar Surface

Microfibrillar-associated protein 4 (MFAP4) is localized to elastic fibers in blood vessels and the interalveolar septa of the lungs and is further present in bronchoalveolar lavage. Mfap4 has been previously suggested to be involved in elastogenesis in the lung. We tested this prediction and aimed to characterize the pulmonary function changes and emphysematous changes that occur in Mfap4-deficient ( Mfap4 −/−) mice. Significant changes included increases in total lung capacity and compliance, which were evident in Mfap4 −/− mice at 6 and 8 mo but not at 3 mo of age. Using in vivo breath-hold gated microcomputed tomography (micro-CT) in 8-mo-old Mfap4 −/− mice, we found that the mean density of the lung parenchyma was decreased, and the low-attenuation area (LAA) was significantly increased by 14% compared with Mfap4 +/+ mice. Transmission electron microscopy (TEM) did not reveal differences in the organization of elastic fibers, and there was no difference in elastin content, but a borderline significant increase in elastin mRNA expression in 3-mo-old mice. Stereological analysis showed that alveolar surface density in relation to the lung parenchyma and total alveolar surface area inside of the lung were both significantly decreased in Mfap4−/− mice by 25 and 15%, respectively. The data did not support an essential role of MFAP4 in pulmonary elastic fiber organization or content but indicated increased turnover in young Mfap4 −/− mice. However, Mfap4 −/− mice developed a spontaneous loss of lung function, which was evident at 6 mo of age, and moderate air space enlargement, with emphysema-like changes.

scholarly journals Molecular Analysis of Fibulin-5 Function during De Novo Synthesis of Elastic Fibers

2007 ◽  
Vol 27 (3) ◽  
pp. 1083-1095 ◽  
Author(s):  
Qian Zheng ◽  
Elaine C. Davis ◽  
James A. Richardson ◽  
Barry C. Starcher ◽  
Tiansen Li ◽  
...  
Keyword(s):  
Calcium Binding ◽  
De Novo ◽  
Elastic Fiber ◽  
Elastic Fibers ◽  
Cellular Behavior ◽  
Fiber Assembly ◽  
Structural Support ◽  
The Matrix ◽  
Epidermal Growth

ABSTRACT Elastic fibers contribute to the structural support of tissues and to the regulation of cellular behavior. Mice deficient for the fibulin-5 gene (fbln5 − / −) were used to further elucidate the molecular mechanism of elastic fiber assembly. Major elastic fiber components were present in the skin of fbln5 − / − mice despite a dramatic reduction of mature elastic fibers. We found that fibulin-5 preferentially bound the monomeric form of elastin through N-terminal and C-terminal elastin-binding regions and to a preexisting matrix scaffold through calcium-binding epidermal growth factor (EGF)-like (CB-EGF) domains. We further showed that adenovirus-mediated gene transfer of fbln5 was sufficient to regenerate elastic fibers and increase elastic fiber-cell connections in vivo. A mutant fibulin-5 lacking the first 28 amino acids of the first CB-EGF domain, however, was unable to rescue elastic fiber defects. Fibulin-5 thus serves as an adaptor molecule between monomeric elastin and the matrix scaffold to aid in elastic fiber assembly. These results also support the potential use of fibulin-5 as a therapeutic agent for the treatment of elastinopathies.

scholarly journals Disruption of NO-cGMP signaling by neonatal hyperoxia impairs relaxation of lung parenchyma

2007 ◽  
Vol 293 (4) ◽  
pp. L1029-L1036 ◽  
Author(s):  
Ramadan B. Sopi ◽  
Musa A. Haxhiu ◽  
Richard J. Martin ◽  
Ismail A. Dreshaj ◽  
Suneel Kamath ◽  
...  
Keyword(s):  
Electrical Field Stimulation ◽  
Lung Parenchyma ◽  
Airway Hyperreactivity ◽  
Neonatal Rat ◽  
Air Exposure ◽  
Rat Pups ◽  
Hyperoxic Exposure ◽  
Cgmp Signaling ◽  
Neonatal Lung ◽  
Neonatal Hyperoxia

Exposure of immature lungs to hyperoxia for prolonged periods contributes to neonatal lung injury and airway hyperreactivity. We studied the role of disrupted nitric oxide-guanosine 3′,5′-cyclic monophosphate (NO-cGMP) signaling in impairing the relaxant responses of lung tissue from hyperoxia-exposed rat pups. Pups were exposed to ≥95% O2 or room air for 7 days starting from days 1, 5, or 14. The animals were killed, lungs were removed, and 1-mm-thick lung parenchymal strips were prepared. Lung parenchymal strips of room air or hyperoxic pups were preconstricted using bethanechol and then graded electrical field stimulation (EFS) was applied to induce relaxation. EFS-induced relaxation of lung parenchymal strips was greater at 7 and 12 days than at 21 days in room air-exposed rat pups. Hyperoxic exposure significantly reduced relaxation at 7 and 12 days but not 21 days compared with room air exposure. NO synthase blockade with Nω-nitro-l-arginine methyl ester diminished relaxant responses in room air but not in hyperoxic pups at 12 days. After incubation with supplemental l-arginine, the relaxation response of hyperoxic strips was restored. cGMP, a key mediator of the NO signaling pathway, also decreased in strips from hyperoxic vs. room air pups and cGMP levels were restored after incubation with supplemental l-arginine. In addition, arginase activity was significantly increased in hyperoxic lung parenchymal strips compared with room air lung parenchymal strips. These data demonstrate disruption of NO-cGMP signaling in neonatal rat pups exposed to hyperoxia and show that bioavailability of the substrate l-arginine is implicated in the predisposition of this model to airway hyperreactivity.

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