Fibroblast growth factor-1 attenuates TGF-β1-induced lung fibrosis

Shimbori, Chiko; Bellaye, Pierre‐Simon; Xia, Jiaji; Gauldie, Jack; Ask, Kjetil; Ramos, Carlos; Becerril, Carina; Pardo, Annie; Selman, Moisés; Kolb, Martin

doi:10.1002/path.4768

Cited by 83 publications

(74 citation statements)

References 51 publications

(73 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, transient upregulation of FGF1 markedly attenuated TGFβ1-induced lung fibrosis in rats when given either concomitantly or post-injury by enhancing AEC proliferation and hyperplasia 86 . In addition, mice engineered to inducibly overexpress FGF10 in the alveolar epithelium during both the inflammatory phase and the more clinically relevant fibrotic phase of the bleomycin injury model showed a strong attenuation of fibrotic scarring in the lungs 87 .…”

Section: Growth Factorsmentioning

confidence: 91%

Emerging therapies for idiopathic pulmonary fibrosis, a progressive age-related disease

Mora

Rojas

Pardo

et al. 2017

Nat Rev Drug Discov

Self Cite

290

212

View full text Add to dashboard Cite

Idiopathic pulmonary fibrosis (IPF) is a fatal age-associated disease that is characterized by progressive and irreversible scarring of the lung. The pathogenesis of IPF is not completely understood and current therapies are limited to those that reduce the rate of functional decline in patients with mild-to-moderate disease. In this context, new therapeutic approaches that substantially improve the survival time and quality of life of these patients are urgently needed. Our incomplete understanding of the pathogenic mechanisms of IPF and the lack of appropriate experimental models that reproduce the key characteristics of the human disease are major challenges. As ageing is a major risk factor for IPF, age-related cell perturbations such as telomere attrition, senescence, epigenetic drift, stem cell exhaustion, loss of proteostasis and mitochondrial dysfunction are becoming targets of interest for IPF therapy. In this Review, we discuss current and emerging therapies for IPF, particularly those targeting age-related mechanisms, and discuss future therapeutic approaches.Fibrosis as a pathogenic mechanism occurs in numerous organs and diseases. Fibrosis results from abnormal tissue repair and is associated with persistent and/or severe tissue damage and cellular stress. Epithelial and/or endothelial injury caused by various insults triggers interrelated wound-healing pathways to restore homeostasis 1 . Failure to adequately contain or eliminate inciting factors can exacerbate inflammation and chronic woundCorrespondence to A.L.M. anamora@pitt.edu. Competing interests statementThe authors declare competing interests: see Web version for details. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript healing responses, resulting in continued tissue damage and inadequate regeneration and, ultimately, fibrosis 2 . Although their aetiology and causative mechanisms differ, the various fibrotic diseases all have abnormal and exaggerated accumulation of extracellular matrix (ECM) components, mainly fibrillar collagens. The resulting fibrosis disturbs the normal architecture of affected organs, which ultimately leads to their dysfunction and failure. Nearly 45% of deaths in the developed world are attributable to some type of chronic fibroproliferative disease, including idiopathic pulmonary fibrosis (IPF) and end-stage fibrotic liver, kidney and heart disease 2 . The progressive nature of these diseases and the absence of effective treatments mean that a better understanding of the cellular and molecular mechanisms that contribute to the development of fibrosis is needed.Although IPF was originally thought to be an inflammation-driven disorder, clinical trials with a combination of anti-inflammatory drugs (prednisone, azathioprine and N-acetyl-Lcysteine (NAC)), failed to improve outcomes and instead increased mortality 3 . In 2014, two drugs, pirfenidone, a drug with poorly understood mechanisms, and nintedanib, a tyrosine kinase inhibitor, were approved for the treatment of IPF ...

show abstract

Section: Growth Factorsmentioning

confidence: 91%

Emerging therapies for idiopathic pulmonary fibrosis, a progressive age-related disease

Mora

Rojas

Pardo

et al. 2017

Nat Rev Drug Discov

Self Cite

290

212

View full text Add to dashboard Cite

show abstract

“…Rats were given intratracheal instillations of TGF-β1 adenovirus (Ad-TGF-β1223/225) or control virus (Ad-DL) was prepared and treated to rats as previously described 17. Rats received 5.0×10 8 plaque-forming unit virus in 300 µL sterile saline intratracheally and were culled on day 7, 14, 21 or 35 by terminal anaesthesia.…”

Section: Methodsmentioning

confidence: 99%

Mechanical stress-induced mast cell degranulation activates TGF-β1 signalling pathway in pulmonary fibrosis

Shimbori

Upagupta

Bellaye

et al. 2019

Thorax

Self Cite

View full text Add to dashboard Cite

BackgroundThe role of mast cells accumulating in idiopathic pulmonary fibrosis (IPF) lungs is unknown.ObjectivesWe investigated the effect of fibrotic extracellular matrix (ECM) on mast cells in experimental and human pulmonary fibrosis.ResultsIn IPF lungs, mast cell numbers were increased and correlated with disease severity (control vs 60%90% vs 60%90% vs FVC<60%, mean difference=−268.6, 95% CI of difference −441.0 to −96.17, p=0.0007). Plasma tryptase levels were increased in IPF and negatively correlated with FVC (control vs FVC<60%, mean difference=−17.12, 95% CI of difference −30.02 to −4.22, p=0.006: correlation curves R=−0.045, p=0.025). In a transforming growth factor (TGF)-β1-induced pulmonary fibrosis model, chymase-positive and tryptase-positive mast cells accumulated in fibrotic lung. Lung tissue was decellularised and reseeded with bone marrow or peritoneum-derived mast cells; cells on fibrotic ECM released more TGF-β1 compared with normal ECM (active TGF-β1: bone marrow-derived mast cell (BMMC)-DL vs BMMC-TGF-β1 p=0.0005, peritoneal mast cell (PMC)-DL vs PMC-TGF-β1 p=0.0003, total TGF-β1: BMMC-DL vs BMMC-TGF-β1 p=0.013, PMC-DL vs PMC-TGF-β1 p=0.001). Mechanical stretch of lungs caused mast cell degranulation; mast cell stabilisers inhibited degranulation (histamine: cont vs doxantrazole p=0.004, β-hexosaminidase: cont vs doxantrazole, mean difference=1.007, 95% CI of difference 0.2700 to 1.744, p=0.007) and TGF-β1 activation (pSmad2/Smad2: cont vs dox p=0.006). Cromoglycate attenuated pulmonary fibrosis in rats (collagen: phosphate-buffered saline (PBS) vs cromoglycate p=0.036, fibrotic area: PBS vs cromoglycate p=0.031).ConclusionThis study suggests that mast cells may contribute to the progression of pulmonary fibrosis.

show abstract

“…These findings taken together thus suggest a critical role for FGF-1 in the development of OA. Interestingly, such a repressive effect of FGF-1 on CCN2 production was strongly implicated by the results of a recent study on lung fibrosis as well (Shimbori et al 2016). According to that study, overexpression of FGF-1 by an adenoviral vector strongly attenuated the TGF-β1-induced lung fibrosis in a rat model in vivo.…”

Section: Discussionmentioning

confidence: 93%

Catabolic effects of FGF-1 on chondrocytes and its possible role in osteoarthritis

El-Seoudi

Kader

Nishida

et al. 2017

J. Cell Commun. Signal.

View full text Add to dashboard Cite

Fibroblast growth factor 1 (FGF-1) is a classical member of the FGF family and is produced by chondrocytes cultured from osteoarthritic patients. Also, this growth factor was shown to bind to CCN family protein 2 (CCN2), which regenerates damaged articular cartilage and counteracts osteoarthritis (OA) in an animal model. However, the pathophysiological role of FGF-1 in cartilage has not been well investigated. In this study, we evaluated the effects of FGF-1 in vitro and its production in vivo by use of an OA model. Treatment of human chondrocytic cells with FGF-1 resulted in marked repression of genes for cartilaginous extracellular matrix components, whereas it strongly induced matrix metalloproteinase 13 (MMP-13), representing its catabolic effects on cartilage. Interestingly, expression of the CCN2 gene was dramatically repressed by FGF-1, which repression eventually caused the reduced production of CCN2 protein from the chondrocytic cells. The results of a reporter gene assay revealed that this repression could be ascribed, at least in part, to transcriptional regulation. In contrast, the gene expression of FGF-1 was enhanced by exogenous FGF-1, indicating a positive feedback system in these cells. Of note, induction of FGF-1 was observed in the articular cartilage of a rat OA model. These results collectively indicate a pathological role of FGF-1 in OA development, which includes an insufficient cartilage regeneration response caused by CCN2 down regulation.

show abstract

Fibroblast growth factor-1 attenuates TGF-β1-induced lung fibrosis

Cited by 83 publications

References 51 publications

Emerging therapies for idiopathic pulmonary fibrosis, a progressive age-related disease

Emerging therapies for idiopathic pulmonary fibrosis, a progressive age-related disease

Mechanical stress-induced mast cell degranulation activates TGF-β1 signalling pathway in pulmonary fibrosis

Catabolic effects of FGF-1 on chondrocytes and its possible role in osteoarthritis

Contact Info

Product

Resources

About