Nox4 mediates TGF-β1-induced retinoblastoma protein phosphorylation, proliferation, and hypertrophy in human airway smooth muscle cells

Sturrock, Anne; Huecksteadt, Thomas P.; Norman, Kimberly G.; Sanders, Karl; Murphy, Thomas M.; Chitano, Pasquale; Wilson, Kimberly; Hoidal, John R.; Kennedy, Thomas P.

doi:10.1152/ajplung.00430.2006

Cited by 120 publications

(103 citation statements)

References 71 publications

(93 reference statements)

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“…The former include plateletderived growth factor (PDGF), epidermal growth factor (EGF), and TGF-b (42-45), whereas the latter include histamine, thrombin, endothelin, and tryptase (46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56). EGF and TGF-b are synthesized by airway epithelial cells (57,58), consistent with the notion that epithelial damage induces production of paracrine growth factors, which stimulate airway smooth muscle growth (Figure 2).…”

Section: Biochemical Mechanisms Of Airway Smooth Muscle Proliferationmentioning

confidence: 57%

Airway Smooth Muscle Growth in Asthma: Proliferation, Hypertrophy, and Migration

Bentley

Hershenson

2008

Proceedings of the American Thoracic Society

158

128

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Increased airway smooth muscle mass is present in fatal and nonfatal asthma. However, little information is available regarding the cellular mechanism (i.e., hyperplasia vs. hypertrophy). Even less information exists regarding the functional consequences of airway smooth muscle remodeling. It would appear that increased airway smooth muscle mass would tend to increase airway narrowing and airflow obstruction. However, the precise effects of increased airway smooth muscle mass on airway narrowing are not known. This review will consider the evidence for airway smooth muscle cell proliferation and hypertrophy in asthma, potential functional effects, and biochemical mechanisms.

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Section: Biochemical Mechanisms Of Airway Smooth Muscle Proliferationmentioning

confidence: 57%

Airway Smooth Muscle Growth in Asthma: Proliferation, Hypertrophy, and Migration

Bentley

Hershenson

2008

Proceedings of the American Thoracic Society

158

128

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“…Studies show that preventing TGF-b1 overexpression or signaling reduces and/or leads to a parallel decline in HASM hypertrophy (89). It is suggested that TGF-b1 may mediate its effects on HASM hypertrophy through the activation of NOX4 (81).…”

Section: Airway Remodeling and Proliferationmentioning

confidence: 99%

Transforming Growth Factor β1 Function in Airway Remodeling and Hyperresponsiveness. The Missing Link?

Ojiaku

Yoo

Panettieri

2017

Am J Respir Cell Mol Biol

100

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The pathogenesis of asthma includes a complex interplay among airway inflammation, hyperresponsiveness, and remodeling. Current evidence suggests that airway structural cells, including bronchial smooth muscle cells, myofibroblasts, fibroblasts, and epithelial cells, mediate all three aspects of asthma pathogenesis. Although studies show a connection between airway remodeling and changes in bronchomotor tone, the relationship between the two remains unclear. Transforming growth factor b1 (TGF-b1), a growth factor elevated in the airway of patients with asthma, plays a role in airway remodeling and in the shortening of various airway structural cells. However, the role of TGF-b1 in mediating airway hyperresponsiveness remains unclear. In this review, we summarize the literature addressing the role of TGF-b1 in airway remodeling and shortening. Through our review, we aim to further elucidate the role of TGF-b1 in asthma pathogenesis and the link between airway remodeling and airway hyperresponsiveness in asthma and to define TGF-b1 as a potential therapeutic target for reducing asthma morbidity and mortality.

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“…For example, NOX4-mediated ROS production in human pulmonary artery smooth muscle cells in response to TGF-β occurs primarily intracellularly, and NOX4 appears to localize to the ER or the nucleus (186). Accordingly, NOX4 activation was associated with intracellular ERK1/2 signaling and phosphorylation of nuclear or ER proteins, such as retinoblastoma protein and eukaryotic translation initiation factor 4E binding protein-1, thereby mediating smooth muscle cell proliferation and hypertrophy (186,193). In contrast, myofibroblasts obtained from patients with iodopathic pulmonary fibrosis were found to produce primarily extracellular H 2 O 2 in response to TGF-β1, and are thereby capable of inducing cell death in neighboring pulmonary epithelial cells, suggesting the association of NOX4 with the plasma membrane as a paracrine signaling molecule (187).…”

Section: Functional Aspects Of Nox In Other Lung Cell Typesmentioning

confidence: 99%

“…Observations of NOX4 induction by TGF-β in pulmonary fibroblasts or smooth muscle cells strongly suggest its importance in pulmonary fibrosis or airway remodeling during chronic lung diseases such as asthma (187,193). Indeed, recent analysis of lung tissues from patients with pulmonary arterial hypertension revealed ã 2.5-fold upregulation of NOX4, which is believed to contribute to oxidant-mediated smooth muscle cell proliferation (81).…”

Section: Other Nox'smentioning

confidence: 99%

NADPH oxidases in lung biology and pathology: Host defense enzymes, and more

Vliet

2008

Free Radical Biology and Medicine

187

192

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The deliberate production of reactive oxygen species (ROS) by phagocyte NADPH oxidase is widely appreciated as a critical component of antimicrobial host defense. Recently, additional homologs of NADPH oxidase (NOX) have been discovered throughout the animal and plant kingdoms, which appear to possess diverse functions in addition to host defense, including cell proliferation, differentiation, and regulation of gene expression. Several of these NOX homologs are also expressed within the respiratory tract, where they participate in innate host defense as well as in epithelial and inflammatory cell signaling and gene expression, and fibroblast and smooth muscle cell proliferation, in response to bacterial or viral infection and environmental stress. Inappropriate expression or activation of NOX/DUOX during various lung pathologies suggests their specific involvement in respiratory disease. This review summarizes the current state of knowledge regarding the general functional properties of mammalian NOX enzymes, and their specific importance in respiratory tract physiology and pathology.

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Nox4 mediates TGF-β1-induced retinoblastoma protein phosphorylation, proliferation, and hypertrophy in human airway smooth muscle cells

Abstract: TP. Nox4 mediates TGF-␤1-induced retinoblastoma protein phosphorylation, proliferation, and hypertrophy in human airway smooth muscle cells.

Cited by 120 publications

References 71 publications

Airway Smooth Muscle Growth in Asthma: Proliferation, Hypertrophy, and Migration

Airway Smooth Muscle Growth in Asthma: Proliferation, Hypertrophy, and Migration

Transforming Growth Factor β1 Function in Airway Remodeling and Hyperresponsiveness. The Missing Link?

NADPH oxidases in lung biology and pathology: Host defense enzymes, and more

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