Disorders of lung matrix remodeling

Chapman, Harold A.

doi:10.1172/jci200420729

Cited by 77 publications

(21 citation statements)

References 100 publications

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“…TGF-b exists in three isoforms [24] and TGF-b 1 is most linked to tissue fibrosis [25]. The ECP-induced stimulation of TGF-b 1 secretion by fibroblasts was dose-dependent, with 10 mg/ml giving the most pronounced effect.…”

Section: Discussionmentioning

confidence: 99%

Eosinophil Cationic Protein Stimulates TGF-β1 Release by Human Lung Fibroblasts In Vitro

et al. 2007

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Eosinophilic inflammation and airway remodeling are features of asthma. Eosinophil cationic protein (ECP) is released by activated eosinophils and transforming growth factor (TGF)-beta(1) has major functions in the fibrotic process. We therefore hypothesized that ECP stimulates TGF-beta(1) release by human lung fibroblasts. Fibroblasts in monolayer displayed a constitutive release of TGF-beta(1), which increased in presence of ECP (436 +/- 60 vs. 365 +/- 48 pg/ml at 48 h; P < 0.01). mRNA expression of TGF-beta(1) was almost twofold in ECP-stimulated fibroblasts. ECP in three-dimensional cultures stimulated both TGF-beta(1) release (180 +/- 61 vs. 137 +/- 54 pg/ml; P < 0.01) and fibroblast-mediated collagen gel contraction (28 vs. 39% of initial gel area at 48 h; P < 0.001). ECP stimulates TGF-beta(1)-release by human lung fibroblasts, suggesting a potential mechanism for eosinophils in the fibrotic response. This may be an important mechanism by which ECP promotes remodeling of extra cellular matrix leading to airway fibrosis in asthmatics.

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Section: Discussionmentioning

confidence: 99%

Eosinophil Cationic Protein Stimulates TGF-β1 Release by Human Lung Fibroblasts In Vitro

et al. 2007

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“…34 IPF is one of the most common forms of interstitial lung diseases, characterized by apoptosis of ATII cells, alveolar fibrin deposition, depressed fibrinolysis, inflammation, myofibroblast accumulation, and progressive loss of lung function as a result of accumulation of extracellular matrix proteins. 2,35,36 Myofibroblasts play a vital role in fibrogenesis after lung injury. The literature suggests that myofibroblasts arise from activation of resident lung fibroblasts, from differentiation of bone-marrowederived stromal cells and also from ATII cells via EMT.…”

Section: Upa-fibrinolytic System In Atii Cell Emtmentioning

confidence: 99%

Role of the Urokinase-Fibrinolytic System in Epithelial–Mesenchymal Transition during Lung Injury

Marudamuthu

Bhandary

Shetty

et al. 2015

The American Journal of Pathology

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Alveolar type II epithelial (ATII) cell injury precedes development of pulmonary fibrosis. Mice lacking urokinase-type plasminogen activator (uPA) are highly susceptible, whereas those deficient in plasminogen activator inhibitor (PAI-1) are resistant to lung injury and pulmonary fibrosis. Epithelial-mesenchymal transition (EMT) has been considered, at least in part, as a source of myofibroblast formation during fibrogenesis. However, the contribution of altered expression of major components of the uPA system on ATII cell EMT during lung injury is not well understood. To investigate whether changes in uPA and PAI-1 by ATII cells contribute to EMT, ATII cells from patients with idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease, and mice with bleomycin-, transforming growth factor β-, or passive cigarette smoke-induced lung injury were analyzed for uPA, PAI-1, and EMT markers. We found reduced expression of E-cadherin and zona occludens-1, whereas collagen-I and α-smooth muscle actin were increased in ATII cells isolated from injured lungs. These changes were associated with a parallel increase in PAI-1 and reduced uPA expression. Further, inhibition of Src kinase activity using caveolin-1 scaffolding domain peptide suppressed bleomycin-, transforming growth factor β-, or passive cigarette smoke-induced EMT and restored uPA expression while suppressing PAI-1. These studies show that induction of PAI-1 and inhibition of uPA during fibrosing lung injury lead to EMT in ATII cells.

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“…Several groups have compelling evidence that new fibroblasts can arise in the lung, liver, and kidney from epithelial structures as a result of a process known as epithelialmesenchymal transition (reviewed in ref. 23). Other studies indicate that BM-derived fibrocytes represent another potential cellular origin for collagen-producing cells (24,25).…”

Section: Important Cellular Culprits Of Fibrosismentioning

confidence: 99%

Infectious disease, the innate immune response, and fibrosis

Meneghin¹,

Hogaboam²

2007

J. Clin. Invest.

178

163

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The unrelenting and destructive progression of most fibrotic responses in the pulmonary, cardiovascular, integumentary, and alimentary systems remains a major medical challenge for which therapies are desperately needed. The pathophysiology of fibrosis remains an enigma, but considerable research and debate surrounds the question of whether chronic inflammation is the key driver of unrestrained wound healing (i.e., the fibrotic response) in these and other organ systems. This Review describes how infectious pathogens, chronic inflammation, and unrestrained fibroproliferation are likely to be part of a dynamic, unrelenting process propelling human fibrotic diseases.

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Disorders of lung matrix remodeling

Cited by 77 publications

References 100 publications

Eosinophil Cationic Protein Stimulates TGF-β1 Release by Human Lung Fibroblasts In Vitro

Eosinophil Cationic Protein Stimulates TGF-β1 Release by Human Lung Fibroblasts In Vitro

Role of the Urokinase-Fibrinolytic System in Epithelial–Mesenchymal Transition during Lung Injury

Infectious disease, the innate immune response, and fibrosis

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