Pulmonary Fibrosis in Response to Environmental Cues and Molecular Targets Involved in Its Pathogenesis

Yoshida, Toshinori; Ohnuma, Aya; Horiuchi, Haruka; Harada, Takanori

doi:10.1293/tox.24.9

Cited by 18 publications

(14 citation statements)

References 154 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, BMPs, particularly BMP-7 and BMP-4, counter TGF- β -mediated fibrotic processes. 50 The balance between TGF- β and BMP signaling may, therefore, be an important determinant of tissue fibrosis after injury. Inhibitors of BMPs have been identified, and may affect this balance.…”

Section: Tgf-β In Sarcoidosis-associated Pfmentioning

confidence: 99%

The clinical and immunologic features of pulmonary fibrosis in sarcoidosis

Patterson¹,

Hogarth²,

Husain³

et al. 2012

Translational Research

View full text Add to dashboard Cite

Sarcoidosis is a multisystem, granulomatous disease that most often affects the lungs. The clinical course is highly variable; many patients undergo spontaneous remission, but up to a third of patients progresses to a chronic disease course. The development of pulmonary fibrosis (PF) in a subset of patients with chronic disease has a negative impact on morbidity and mortality. While sarcoidosis-associated PF can be progressive, it is often referred to as “burnt out” disease, a designation reflecting inactive granulomatous inflammation. The immune mechanisms of sarcoidosis-associated PF are not well understood. It is not clear if fibrotic processes are active from the onset of sarcoidosis in predisposed individuals, or whether a profibrotic state develops as a response to ongoing inflammation. Transforming growth factor β (TGF-β) is an important profibrotic cytokine, and in sarcoidosis, distinct genotypes of TGF-β have been identified in those with PF. The overall cytokine profile in sarcoidosis-associated PF has not been well characterized, although a transition from a T helper 1 to a T helper 2 signature has been proposed. Macrophages have important regulatory interactions with fibroblasts, and the role of alveolar macrophages in sarcoidosis-associated PF is a compelling target for further study. Elucidating the natural history of sarcoidosis-associated PF will inform our understanding of the fundamental derangements, and will enhance prognostication and the development of therapeutic strategies.

show abstract

Section: Tgf-β In Sarcoidosis-associated Pfmentioning

confidence: 99%

The clinical and immunologic features of pulmonary fibrosis in sarcoidosis

Patterson¹,

Hogarth²,

Husain³

et al. 2012

Translational Research

View full text Add to dashboard Cite

show abstract

“…As major effectors of the innate immune system of the body, alveolar macrophages interact with other cells in the airways and alveoli immediately after birth, resulting in generation of intracellular signalling cascades, leading to various effects or functions that make up the initial immune response in the lungs. Alveolar macrophages have been demonstrated to play a key role in the pathogenesis of pulmonary fibrosis by releasing a variety of cytokines and inflammatory mediators [16,17] …”

Section: Discussionmentioning

confidence: 99%

“…Alveolar macrophages have been demonstrated to play a key role in the pathogenesis of pulmonary fibrosis by releasing a variety of cytokines and inflammatory mediators. [16,17] Bleomycin A5 is considered as a toxic substance which induces pulmonary fibrosis in both humans and other animals. The intratracheal instillation of bleomycin A5 into rats results in a substantial inflammatory reaction in the lung followed by the development of pulmonary fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Antifibrosis effects of triterpene acids of Eriobotrya japonica (Thunb.) Lindl. leaf in a rat model of bleomycin-induced pulmonary fibrosis

Yang

Huang

et al. 2012

Journal of Pharmacy and Pharmacology

View full text Add to dashboard Cite

show abstract

“…Pulmonary fibrosis is characterised by the thickening of alveolar septa, accompanied by an over-deposition of extracellular matrix (ECM), which results in reduced gas exchange capacity. It is a very heterogeneous condition and has a high mortality rate (1). Viral infections, environmental toxins and chemotherapeutic drugs can lead to pulmonary fibrosis (1)(2)(3).…”

Section: Introductionmentioning

confidence: 99%

Lung Fibrosis: Drug Screening and Disease Biomarker Identification with a Lung Slice Culture Model and Subtracted cDNA Library

Guo

Lok

et al. 2014

Altern Lab Anim

View full text Add to dashboard Cite

Pulmonary fibrosis is a progressive and irreversible disorder with no appropriate cure. A practical and effective experimental model that recapitulates the disease will greatly benefit the research community and, ultimately, patients. In this study, we tested the lung slice culture (LSC) system for its potential use in drug screening and disease biomarker identification. Fibrosis was induced by treating rat lung slices with 1ng/ml TGF-ß1 and 2.5μM CdCl2, quantified by measuring the content of hydroxyproline, and confirmed by detecting the expression of collagen type III alpha 1 (Col3α1) and connective tissue growth factor (CTGF) genes. The anti-fibrotic effects of pirfenidone, spironolactone and eplerenone were assessed by their capability to reduce hydroxyproline content. A subtractive hybridisation technique was used to create two cDNA libraries (subtracted and unsubtracted) from lung slices. The housekeeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was employed to assess the subtraction efficiency of the subtracted cDNA library. Clones from the two libraries were sequenced and the genes were identified by performing a BLAST search on the NCBI GenBank database. Furthermore, the relevance of the genes to fibrosis formation was verified. The results presented here show that fibrosis was effectively induced in cultured lung slices, which exhibited significantly elevated levels of hydroxyproline and Col3α1/CTGF gene expression. Several inhibitors have demonstrated their anti-fibrotic effects by significantly reducing hydroxyproline content. The subtracted cDNA library, which was enriched for differentially expressed genes, was used to successfully identify genes associated with fibrosis. Collectively, the results indicate that our LSC system is an effective model for the screening of drug candidates and for disease biomarker identification.

show abstract

Pulmonary Fibrosis in Response to Environmental Cues and Molecular Targets Involved in Its Pathogenesis

Cited by 18 publications

References 154 publications

The clinical and immunologic features of pulmonary fibrosis in sarcoidosis

The clinical and immunologic features of pulmonary fibrosis in sarcoidosis

Antifibrosis effects of triterpene acids of Eriobotrya japonica (Thunb.) Lindl. leaf in a rat model of bleomycin-induced pulmonary fibrosis

Lung Fibrosis: Drug Screening and Disease Biomarker Identification with a Lung Slice Culture Model and Subtracted cDNA Library

Contact Info

Product

Resources

About