Tropoelastin modulates TGF-β1-induced expression of VEGF and CTGF in airway smooth muscle cells

Reddel, Caroline J.; Cultrone, Daniele; Rnjak‐Kovacina, Jelena; Weiss, Anthony S.; Burgess, Janette K.

doi:10.1016/j.matbio.2013.04.003

Cited by 17 publications

(16 citation statements)

References 40 publications

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“…Protein kinases ERK1/2 are involved in MMP regulation (Duca et al, 2007). TE modulates the release of vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) from SMC stimulated by TGF-β1 (Reddel et al, 2013). …”

Section: Regulatory Role Of Elastinmentioning

confidence: 99%

Elastin in the Liver

Kanta

2016

Front. Physiol.

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A characteristic feature of liver cirrhosis is the accumulation of large amounts of connective tissue with the prevailing content of type I collagen. Elastin is a minor connective tissue component in normal liver but it is actively synthesized by hepatic stellate cells and portal fibroblasts in diseased liver. The accumulation of elastic fibers in later stages of liver fibrosis may contribute to the decreasing reversibility of the disease with advancing time. Elastin is formed by polymerization of tropoelastin monomers. It is an amorphous protein highly resistant to the action of proteases that forms the core of elastic fibers. Microfibrils surrounding the core are composed of fibrillins that bind a number of proteins involved in fiber formation. They include microfibril-associated glycoproteins (MAGPs), microfibrillar-associated proteins (MFAPs) and fibulins. Lysyl oxidase (LOX) and lysyl oxidase-like proteins (LOXLs) are responsible for tropoelastin cross-linking and polymerization. TGF-β complexes attached to microfibrils release this cytokine and influence the behavior of the cells in the neighborhood. The role of TGF-β as the main profibrotic cytokine in the liver is well-known and the release of the cytokines of TGF-β superfamily from their storage in elastic fibers may affect the course of fibrosis. Elastic fibers are often studied in the tissues where they provide elasticity and resilience but their role is no longer viewed as purely mechanical. Tropoelastin, elastin polymer and elastin peptides resulting from partial elastin degradation influence fibroblastic and inflammatory cells as well as angiogenesis. A similar role may be performed by elastin in the liver. This article reviews the results of the research of liver elastic fibers on the background of the present knowledge of elastin biochemistry and physiology. The regulation of liver elastin synthesis and degradation may be important for the outcome of liver fibrosis.

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Section: Regulatory Role Of Elastinmentioning

confidence: 99%

Elastin in the Liver

Kanta

2016

Front. Physiol.

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“…Elastin remodeling may be angiogenic by one of several mechanisms (20,32,33). To define whether lung elastase activity was associated with angiogenesis, we stained in situ zymography sections for angiogenin.…”

Section: Consistent With Previous Quantitative Data By Immunohistochmentioning

confidence: 99%

“…Reduced matrix metalloproteinase (MMP)-2 and MMP14 activity impairs alveolar septation (4,30), and pulmonary epithelial cells (30), vascular cells (37), and macrophages (26) all remodel lung matrix during saccular and alveolar lung development. Because elastin plays a critical mechano-developmental role in the lung (1), and remodeling of elastin is angiogenic (31)(32)(33), we asked whether elastin remodeling might provide a mechanistic link between matrix remodeling, alveolar growth, and microvascular expansion.…”

mentioning

confidence: 99%

“…First, elastin degradation products containing the valine-glycine-valine-alanine-glycine-proline motif may directly stimulate angiogenesis as they do in cancers of some elastin-rich tissues (31,33). Second, elastin remodeling may release elastin-bound vascular endothelial growth factor as occurs in proximal airways (32). Third, elastin fibers may serve as a scaffold for microvascular growth as they do in the mesentery during repair following direct injury (5).…”

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confidence: 99%

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Dynamic expression of chymotrypsin-like elastase 1 over the course of murine lung development

Liu

Young

Varisco

2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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-Postnatal lung development requires coordination of three processes (surface area expansion, microvascular growth, and matrix remodeling). Because normal elastin structure is important for lung morphogenesis, because physiological remodeling of lung elastin has never been defined, and because elastin remodeling is angiogenic, we sought to test the hypothesis that, during lung development, elastin is remodeled in a defined temporal-spatial pattern, that a novel protease is associated with this remodeling, and that angiogenesis is associated with elastin remodeling. By elastin in situ zymography, lung elastin remodeling increased 24-fold between embryonic day (E) 15.5 and postnatal day (PND) 14. Remodeling was restricted to major vessels and airways on PND1 with a sevenfold increase in alveolar wall elastin remodeling from PND1 to PND14. By inhibition assays and literature review, we identified chymotrypsin-like elastase 1 (CELA1) as a potential mediator of elastin remodeling. CELA1 mRNA levels increased 12-fold from E15.5 to PND9, and protein levels increased 3.4-fold from E18.5 to PND9. By costaining experiments, the temporal-spatial pattern of CELA1 expression matched that of elastin remodeling, and 58 -85% of CELA1 ϩ cells were Ͻ10 m from an elastase signal. An association between elastin remodeling and angiogenesis was tested by similar methods. At PND7 and PND14, 60 -95% of angiogenin ϩ cells were associated with elastin remodeling. Both elastase inhibition and CELA1 silencing impaired angiogenesis in vitro. Our data defines the temporal-spatial pattern of elastin remodeling during lung development, demonstrates an association of this remodeling with CELA1, and supports a role for elastin remodeling in regulating angiogenesis. matrix remodeling; elastin; pulmonary vascular development THREE COORDINATED PROCESSES occur during the saccular and alveolar stages of lung development that are critical to meeting the metabolic demands of ex utero life. Airway branching and septation dramatically increase gas exchange surface area, expansion of the pulmonary microvasculature increases perfusion capacity to match this increased surface area, and matrix remodeling and epithelial thinning increase gas diffusion capacity. Multiple studies have demonstrated that these three processes are intertwined. Microvascular development is necessary for alveolar septation (21), and models of impaired alveolar septation have marked pruning of the pulmonary vasculature (24). Reduced matrix metalloproteinase (MMP)-2 and MMP14 activity impairs alveolar septation (4, 30), and pulmonary epithelial cells (30), vascular cells (37), and macrophages (26) all remodel lung matrix during saccular and alveolar lung development. Because elastin plays a critical mechano-developmental role in the lung (1), and remodeling of elastin is angiogenic (31-33), we asked whether elastin remodeling might provide a mechanistic link between matrix remodeling, alveolar growth, and microvascular expansion.

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“…Several inflammatory mediators have been proven to play important roles in airway remodeling. The cytokine transforming growth factor β1 (TGF-β1) has been reported to stimulate the proliferation and migration of ASMCs, as well as induce ECM protein synthesis and profibrotic differentiation of ASMCs, thereby promoting airway remodeling [5].…”

Section: Introductionmentioning

confidence: 99%

Eupatilin alleviates airway remodeling via regulating phenotype plasticity of airway smooth muscle cells

Ren

Wang

et al. 2020

Bioscience Reports

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Childhood asthma is a common chronic airway disease, and its severe form remains a challenge. Eupatilin is a bioactive natural flavone that has been found to possess potential anti-asthma activity. However, the roles of eupatilin in asthma remain to be elucidated. In the present study, airway smooth muscle cells (ASMCs) were applied for the in vitro investigation since their phenotype plasticity make great contribution to airway remodeling during asthma pathogenesis. Our results showed that eupatilin suppressed the transforming growth factor β1 (TGF-β1)-induced proliferation and migration of ASMCs. Exposure of ASMCs to eupatilin increased the expressions of contractile markers smooth muscle α-actin (α-SMA) and myocardin, whereas expressions of extracellular matrix (ECM) proteins type I collagen (Coll I) and fibronectin were reduced. Furthermore, eupatilin treatment reversed the activation of nuclear factor-κ B (NF-κB), signal transducer and activator of transcription 3 (STAT3) and AKT pathways caused by TGF-β1 in ASMCs. These findings suggested that eupatilin might attenuate airway remodeling via regulating phenotype plasticity of ASMCs.

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Tropoelastin modulates TGF-β1-induced expression of VEGF and CTGF in airway smooth muscle cells

Cited by 17 publications

References 40 publications

Elastin in the Liver

Elastin in the Liver

Dynamic expression of chymotrypsin-like elastase 1 over the course of murine lung development

Eupatilin alleviates airway remodeling via regulating phenotype plasticity of airway smooth muscle cells

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