Transforming growth factor beta 1 gene expression in human airways.

Aubert, John‐David; Dalal, Bakul I.; Bai, Tony R.; Roberts, Clive J.; Hayashi, Seiji; Hogg, James C.

doi:10.1136/thx.49.3.225

Cited by 121 publications

(84 citation statements)

References 46 publications

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“…Although a connection between TGF-β polymorphisms and serum levels was initially presumed based on a few publications, subsequent studies in larger and more heterogeneous populations have not consistently shown this association (37)(38)(39)(40). Immunohistochemical studies of COPD lung specimens show evidence of enhanced TGF-β signaling predominantly in the airway compartment (41)(42)(43). Gene expression studies from lung specimens of patients with COPD demonstrate enhanced activation of TGF-β pathways that may well be stage and compartment dependent (44)(45)(46).…”

Section: Figurementioning

confidence: 99%

Angiotensin receptor blockade attenuates cigarette smoke–induced lung injury and rescues lung architecture in mice

et al. 2012

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Chronic obstructive pulmonary disease (COPD) is a prevalent smoking-related disease for which no diseasealtering therapies currently exist. As dysregulated TGF-β signaling associates with lung pathology in patients with COPD and in animal models of lung injury induced by chronic exposure to cigarette smoke (CS), we postulated that inhibiting TGF-β signaling would protect against CS-induced lung injury. We first confirmed that TGF-β signaling was induced in the lungs of mice chronically exposed to CS as well as in COPD patient samples. Importantly, key pathological features of smoking-associated lung disease in patients, e.g., alveolar injury with overt emphysema and airway epithelial hyperplasia with fibrosis, accompanied CS-induced alveolar cell apoptosis caused by enhanced TGF-β signaling in CS-exposed mice. Systemic administration of a TGF-β-specific neutralizing antibody normalized TGF-β signaling and alveolar cell death, conferring improved lung architecture and lung mechanics in CS-exposed mice. Use of losartan, an angiotensin receptor type 1 blocker used widely in the clinic and known to antagonize TGF-β signaling, also improved oxidative stress, inflammation, metalloprotease activation and elastin remodeling. These data support our hypothesis that inhibition of TGF-β signaling through angiotensin receptor blockade can attenuate CS-induced lung injury in an established murine model. More importantly, our findings provide a preclinical platform for the development of other TGF-β-targeted therapies for patients with COPD.

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Section: Figurementioning

confidence: 99%

Angiotensin receptor blockade attenuates cigarette smoke–induced lung injury and rescues lung architecture in mice

et al. 2012

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“…No studies have yet addressed this question directly. However, in a study of TGF-β 1 gene expression in human airways [22], no difference was found in TGF-β 1 gene expression between smokers and nonsmokers. Furthermore, we made similar observations in mice with no exposure to smoke.…”

Section: Cellular Localization Of Tgf-β 1 and Tgf-β 3 Mrna Transcriptmentioning

confidence: 99%

Diverse cellular TGF-beta 1 and TGF-beta 3 gene expression in normal human and murine lung

Coker¹,

Guy²,

Shahzeidi³

et al. 1996

Eur Respir J

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D Di iv ve er rs se e c ce el ll lu ul la ar r T TG GF F--β 1 1 a an nd d T TG GF F--β 3 3 g ge en ne e e ex xp pr re es ss si io on n i in n n no or rm ma al l h hu um ma an n a an nd d m mu ur ri in ne e l lu un ng g This procedure was technically simple, providing excellent resolution. TGF-β 1 and TGF-β 3 messenger ribonucleic acid (mRNA) transcripts were detected in a wide variety of cells. In human lung, mRNA for both isoforms was localized to bronchiolar epithelium and alveolar macrophages. TGF-β 1 , but not TGF-β 3 mRNA was detected in mesenchymal and endothelial cells. In murine tissue, TGF-β 1 , mRNA was localized to bronchiolar epithelium, Clara cells, mesenchymal cells, pulmonary endothelium and alveolar cells, including macrophages. TGF-β 3 mRNA was similarly distributed but not detected in endothelium.In summary, using a nonisotopic technique in lung tissue, we have detailed the cells expressing the transforming growth factor-β 1 and β 3 genes in human and murine lung. There was widespread expression of these cytokines in normal lung consistent with autocrine or paracrine roles in regulating cellular turnover, immune defence and matrix protein metabolism.

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“…Active TGF-b1 is found to be elevated in the bronchoalveolar lavage fluid (17) and in bronchial biopsy samples (18) taken from subjects with asthma. In addition, TGF-b1 expression is elevated in the bronchial epithelium (34), submucosa, subepithelial connective tissue, subepithelium (35), and ASM (35) of subjects with asthma (18). Although it is unclear which structural cell produces the majority of TGF-b1 in the airway, epithelial-derived TGF-b1 is suggested to be an important contributor to asthma pathogenesis (36).…”

Section: Tgf-b1 and Airway Diseasementioning

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

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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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Transforming growth factor beta 1 gene expression in human airways.

Abstract: TGF-fl, was localised to specific cell types in these lungs by immunohistochemical analysis using polyclonal antibodies specific for intracellular and extracellular TGF-fi,.

Cited by 121 publications

References 46 publications

Angiotensin receptor blockade attenuates cigarette smoke–induced lung injury and rescues lung architecture in mice

Angiotensin receptor blockade attenuates cigarette smoke–induced lung injury and rescues lung architecture in mice

Diverse cellular TGF-beta 1 and TGF-beta 3 gene expression in normal human and murine lung

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

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