The Myofibroblast in Pulmonary Fibrosis*

Phan, Sem H.

doi:10.1378/chest.122.6_suppl.286s

Cited by 469 publications

(454 citation statements)

References 13 publications

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“…1 Fibrosis results from an amplification of the normal wound healing response, in which fibroblasts proliferate, differentiate to myofibroblasts, and deposit collagen to rebuild damaged tissue. [2][3][4][5] In fibrosis, an imbalance exists between the production of extracellular matrix components (eg, fibronectin and collagen I) and their degradation. [1][2][3][5][6][7] In certain organs, such as the eye and lung, fibrosis can result in complete failure of tissue function and significant morbidity.…”

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confidence: 99%

“…5,12 This process thickens and stiffens the alveolar walls, interfering with gas exchange and ventilation. [3][4][5]7,13 IPF is a progressive disease, with poor prognosis and a median survival of only 2 to 5 years from the time of diagnosis. 12 The consequences of both ocular and pulmonary fibrosis are severe, and effective clinical treatments are urgently needed, but not currently available.…”

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confidence: 99%

“…2,5,12 Myofibroblasts are also a major source of extracellular matrix proteins, including collagen and fibronectin. 3,6,12,13 Because of their prominent role in the fibrotic response, myofibroblast differentiation is a promising target for the development of novel antifibrotic therapies. 12 We have used transforming growth factor-␤1 (TGF␤1) to stimulate myofibroblast differentiation in primary cultures of human fibroblasts.…”

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confidence: 99%

“…12 We have used transforming growth factor-␤1 (TGF␤1) to stimulate myofibroblast differentiation in primary cultures of human fibroblasts. [3][4][5]12,14,15 This serves as a useful model system for the identification of potential small molecule inhibitors of myofibroblast differentiation. 12 The results of many studies support the idea that TGF␤1, produced during the normal wound healing response, is a master regulator of fibrosis.…”

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confidence: 99%

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The Aryl Hydrocarbon Receptor Ligand ITE Inhibits TGFβ1-Induced Human Myofibroblast Differentiation

Lehmann

Xia

Kulkarni

et al. 2011

The American Journal of Pathology

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Fibrosis can occur in any human tissue when the normal wound healing response is amplified. Such amplification results in fibroblast proliferation, myofibroblast differentiation, and excessive extracellular matrix deposition. Occurrence of these sequelae in organs such as the eye or lung can result in severe consequences to health. Unfortunately, medical treatment of fibrosis is limited by a lack of safe and effective therapies. These therapies may be developed by identifying agents that inhibit critical steps in fibrotic progression; one such step is myofibroblast differentiation triggered by transforming growth factor-␤1 (TGF␤1). In this study, we demonstrate that TGF␤1-induced myofibroblast differentiation is blocked in human fibroblasts by a candidate endogenous aryl hydrocarbon receptor (AhR) ligand 2-(1=H-indole-3=-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE). Our data show that ITE disrupts TGF␤1 signaling by inhibiting the nuclear translocation of Smad2/3/4. Although ITE functions as an AhR agonist, and biologically persistent AhR agonists, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, cause severe toxic effects, ITE exhibits no toxicity. Interestingly, ITE effectively inhibits TGF␤1-driven myofibroblast differentiation in AhR ؊/؊ fibroblasts: Its ability to inhibit TGF␤1 signaling is AhR independent. As supported by the results of this study, the small molecule ITE inhibits myofibroblast differentiation and may be useful clinically as an antiscarring agent.

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confidence: 99%

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confidence: 99%

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confidence: 99%

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The Aryl Hydrocarbon Receptor Ligand ITE Inhibits TGFβ1-Induced Human Myofibroblast Differentiation

Lehmann

Xia

Kulkarni

et al. 2011

The American Journal of Pathology

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“…The latter causes changes in lung architecture resulting in increased pulmonary vascular resistance and/or lung fibrosis (Mann and Oakley, 2013). Pulmonary fibrosis is characterised by the deposition of excessive amounts of the extracellular matrix protein, collagen, as well as increases in cells associated with collagen synthesis and inflammation (Sime and O'Reilly 2001;Phan, 2002;Blaauboer et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Sibutramine, a serotonin–norepinephrine reuptake inhibitor, causes fibrosis in rats

Oberholzer

Schoor

Bester

2015

Environmental Toxicology and Pharmacology

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Sibutramine hydrochloride monohydrate is a weight loss agent indicated for the treatment of obesity. Although it has been banned from most markets, studies are still relevant as it is often a hidden ingredient in herbal and over the counter slimming products. Sibutramine induces liver fibrosis with steatosis in female Sprague-Dawley rats fed a high-energy diet without significant weight gain. In this study, using the same animal model, the effect of Sibutramine on lung morphology was investigated using histological evaluation of the terminal bronchiole and transmission electron microscopy evaluation of the respiratory tissue. From these results Sibutramine was found to induce lung fibrosis in Sprague-Dawley rats as increased collagen synthesis, mast cell accumulation and aggregates of Bronchus Associated Lymphoid Tissue (BALT) in the terminal bronchiole as well as increased collagen deposition in the respiratory tissue was seen.

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Dual Barrier‐Penetrating Inhaled Nanoparticles for Enhanced Idiopathic Pulmonary Fibrosis Therapy

Yang,

Han,

Tang

et al. 2024

Adv Funct Materials

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Idiopathic pulmonary fibrosis (IPF) is an age‐related pulmonary interstitial disease with unclear etiology that poses a serious threat to human health. IPF interventions in clinical settings mainly involve oral medications, such as nintedanib (NIN), which exhibit limited accumulation in the lungs and neglect the epithelial micro‐environment. Inhalation is an efficient route for the treatment of pulmonary diseases. However, the mucus barrier in the trachea and the extracellular matrix (ECM) barrier in the interstitium are the two main obstacles to inhaled therapeutic agent delivery. Therefore, in this study, dual barrier‐penetrating inhaled liposomes (AN‐TR) are constructed utilizing tris‐(2‐carboxyethyl)‐phosphine (TCEP) and l‐arginine to penetrate the mucus and ECM barriers, respectively. This approach facilitates the thorough and uniform distribution of NIN and navitoclax (ABT‐263) across all five lung lobes. Furthermore, ABT‐263 can remove the senescent epithelial cells in the trachea and alveoli, thereby improving the efficiency of NIN for IPF treatment. This study suggests dual barrier‐penetrating inhaled liposomes as efficient noninvasive vehicles for first‐line clinical medications to improve the efficacy of IPF treatment.

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The Myofibroblast in Pulmonary Fibrosis*

Cited by 469 publications

References 13 publications

The Aryl Hydrocarbon Receptor Ligand ITE Inhibits TGFβ1-Induced Human Myofibroblast Differentiation

The Aryl Hydrocarbon Receptor Ligand ITE Inhibits TGFβ1-Induced Human Myofibroblast Differentiation

Sibutramine, a serotonin–norepinephrine reuptake inhibitor, causes fibrosis in rats

Dual Barrier‐Penetrating Inhaled Nanoparticles for Enhanced Idiopathic Pulmonary Fibrosis Therapy

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