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

Coker, RK; Guy, Laurent; Shahzeidi, Shahriar; Na, Hernández-Rodríguez; Pantelidis, P; Bois, RM du; Jeffery, P. K.; McAnulty, Robin J.

doi:10.1183/09031936.96.09122501

Cited by 89 publications

(64 citation statements)

References 27 publications

(28 reference statements)

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“…In normal lung tissues, TGF-β1 and -β3 are expressed in a variety of cells, most profoundly in bronchial epithelium, alveolar macrophages, mesenchymal, and endothelial cells (Coker et al, 1996). In bleomycin fibrosis, TGF-β1 was shown to be upregulated with maximal expression after 10 days.…”

Section: Discussionmentioning

confidence: 98%

Progressive pulmonary fibrosis is mediated by TGF-β isoform 1 but not TGF-β3

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Bonniaud

Maaß

et al. 2008

The International Journal of Biochemistry & Cell Biology

154

114

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Tissue repair is a well orchestrated biological process involving numerous soluble mediators, and an imbalance between these factors may result in impaired repair and fibrosis. Transforming growth factor (TGF) β is a key profibrotic element in this process and it is thought that its three isoforms act in a similar way. Here, we report that TGF-β3 administered to rat lungs using transient overexpression initiates profibrotic effects similar to those elicited by TGF-β1, but causes less severe and progressive changes. The data suggest that TGF-β3 does not lead to inhibition of matrix degradation in the same way as TGF-β1, resulting in non-fibrotic tissue repair. Further, TGF-β3 is able to downregulate TGF-β1 induced gene expression, suggesting a regulatory role of TGF-β3. TGF-β3 overexpression results in an upregulation of Smad proteins similar to TGF-β1, but is less efficient in inducing the ALK 5 and TGF-β type II receptor (TβRII). We provide evidence that this difference may contribute to the progressive nature of TGF-β1 induced fibrotic response, in contrast to the limited fibrosis observed following TGF-β3 overexpression. TGF-β3 is important in "normal wound healing", but is outbalanced by TGF-β1 in "fibrotic wound healing" in the lung.

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Section: Discussionmentioning

confidence: 98%

Progressive pulmonary fibrosis is mediated by TGF-β isoform 1 but not TGF-β3

Ask

Bonniaud

Maaß

et al. 2008

The International Journal of Biochemistry & Cell Biology

154

114

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“…By contrast, TGF-β1 protein levels remain unchanged during this initial period despite increased mRNA levels [107] Consequently, recent studies have focused on the antifibrotic potential of selectively targeting TGF-β2 for the prevention of progressive renal disease [108]. However, in diabetes, the pro-fibrotic role for all 3 isoforms [109] supports efforts to neutralize TGF-β1, TGF-β2…”

Section: Therapeutic Interventionmentioning

confidence: 99%

The role of TGF-β and epithelial-to mesenchymal transition in diabetic nephropathy

Hills

Squires

2011

Cytokine & Growth Factor Reviews

172

187

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Transforming Growth Factor-beta (TGF-β) is a pro-sclerotic cytokine widely associated with the development of fibrosis in diabetic nephropathy. Central to the underlying pathology of tubulointerstitial fibrosis is epithelial-to-mesenchymal transition (EMT), or the trans-differentiation of tubular epithelial cells into myofibroblasts. This process is accompanied by a number of key morphological and phenotypic changes culminating in detachment of cells from the tubular basement membrane and migration into the interstitium. Ultimately these cells reside as activated myofibroblasts and further exacerbate the state of fibrosis. A large body of evidence supports a role for TGF-β and downstream Smad signaling in the development and progression of renal fibrosis. Here we discuss a role for TGF-β as the principle effector in the development of renal fibrosis in diabetic nephropathy, focusing on the role of the TGF-β1 isoform and its downstream signaling intermediates, the Smad proteins. Specifically we review evidence for TGF-β1 induced EMT in both the proximal and distal regions of the nephron and describe potential therapeutic strategies that may target TGF-β1 activity.

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“…One of these, TGF-b, has a complex role in the pathogenesis of severe asthma (35). It is produced by several cell types, including epithelial cells, eosinophils, macrophages, fibroblasts, and helper T cells (36,37), and is involved in epithelial transformation, subepithelial fibrosis, airway smooth muscle remodeling, microvascular changes, mucus production, and both suppressing and activating inflammatory cytokines (38)(39)(40)(41). TGF-b 1 is a major regulator as well as effector in the immune response.…”

Section: C/fpomentioning

confidence: 99%

Airway Inflammation after Bronchial Thermoplasty for Severe Asthma

et al. 2015

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Rationale: Bronchial thermoplasty is an alternative treatment for patients with severe, uncontrolled asthma in which the airway smooth muscle is eliminated using radioablation. Although this emerging therapy shows promising outcomes, little is known about its effects on airway inflammation.Objectives: We examined the presence of bronchoalveolar lavage cytokines and expression of smooth muscle actin in patients with severe asthma before and in the weeks after bronchial thermoplasty.Methods: Endobronchial biopsies and bronchoalveolar lavage samples from 11 patients with severe asthma were collected from the right lower lobe before and 3 and 6 weeks after initial bronchial thermoplasty. Samples were analyzed for cell proportions and cytokine concentrations in bronchoalveolar lavage and for the presence of a-SMA in endobronchial biopsies.Measurements and Main Results: a-SMA expression was decreased in endobronchial biopsies of 7 of 11 subjects by Week 6. In bronchoalveolar lavage fluid, both transforming growth factor-b 1 and regulated upon activation, normal T-cell expressed and secreted (RANTES)/CCL5 were substantially decreased 3 and 6 weeks post bronchial thermoplasty in all patients. The cytokine tumor-necrosisfactor-related apoptosis-inducing ligand (TRAIL), which induces apoptosis in several cell types, was increased in concentration both 3 and 6 weeks post bronchial thermoplasty.Conclusions: Clinical improvement and reduction in a-SMA after bronchial thermoplasty in severe, uncontrolled asthma is associated with substantial changes in key mediators of inflammation. These data confirm the substantial elimination of airway smooth muscle post thermoplasty in the human asthmatic airway and represent the first characterization of significant changes in airway inflammation in the first weeks after thermoplasty.

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

Cited by 89 publications

References 27 publications

Progressive pulmonary fibrosis is mediated by TGF-β isoform 1 but not TGF-β3

Progressive pulmonary fibrosis is mediated by TGF-β isoform 1 but not TGF-β3

The role of TGF-β and epithelial-to mesenchymal transition in diabetic nephropathy

Airway Inflammation after Bronchial Thermoplasty for Severe Asthma

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