RETRACTED: Discoidin Domain Receptor 1 Contributes to the Survival of Lung Fibroblast in Idiopathic Pulmonary Fibrosis

Matsuyama, Wataru; Watanabe, Masaki; Shirahama, Yuko; Mitsuyama, Hideo; Higashimoto, Ikkou; Osame, Mitsuhiro; Arimura, Kimiyoshi

doi:10.2353/ajpath.2006.050801

Cited by 23 publications

(22 citation statements)

References 49 publications

(61 reference statements)

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“…on May 10, 2018. by guest www.bloodjournal.org From MD), as previously reported. [10][11][12][13][14][15] Additionally, tyrosine phosphorylation of DDR1 and Shc recruitment were analyzed by Western blotting using mouse monoclonal antiphosphotyrosine IgGs (4G10; Upstate Biotechnology) or mouse monoclonal anti-Shc antibodies (R&D Systems, Minneapolis, MN), followed by sheep anti-mouse IgGs coupled with horseradish peroxidase (Amersham). The peroxidase activity was visualized using the enhanced chemiluminescence detection system (Amersham).…”

Section: Western Blot Analysismentioning

confidence: 99%

“…10 In addition, we have recently found that DDR1 conferred protection to the pulmonary fibroblasts from Fas ligand-induced apoptosis. 11 These findings led us to hypothesize that DDR1 might contribute to the prolonged survival of eosinophils in CSS.…”

Section: Introductionmentioning

confidence: 99%

“…9 Five DDR1 isoforms (a, b, c, d, and e) can be generated by alternative splicing of the DDR1 gene, and only 2 isoforms (DDR1a and DDR1b) have been reported to be functional. [10][11][12][13][14][15] We have previously reported that in vitro DDR1 expression could be induced in human leukocytes. 13 The in vivo tissue-infiltrating leukocytes express DDR1 also.…”

Section: Introductionmentioning

confidence: 99%

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Discoidin domain receptor 1 contributes to eosinophil survival in an NF-κB–dependent manner in Churg-Strauss syndrome

Matsuyama

Mitsuyama

Ono

et al. 2006

Blood

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Churg-Strauss syndrome (CSS) is a systemic disease that shows marked eosinophilia along with eosinophil infiltration in the tissue. Prolonged eosinophil survival plays an important role in the pathogenesis of CSS; however, its detailed molecular mechanism remains unclear. Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase, and its ligand is collagen. DDR1 was expressed in human leukocytes and fibroblasts, and it plays an important role in leukocyte cytokine production and fibroblast survival in an NF-κB–dependent manner. In this study, we examined in vitro and in vivo eosinophil DDR1 expression and its function in CSS patients. The expression level of DDR1 was significantly higher in the eosinophils of CSS patients, and the predominant isoform was DDR1b. Immunohistochemical findings revealed that the tissue-infiltrating eosinophils expressed endogenous DDR1. In CSS patients, DDR1 activation inhibited Fas agonistic antibody–induced apoptosis and up-regulated Fas agonistic antibody–induced cytokine production of eosinophils in an NF-κB–dependent manner. Suppression of DDR1 expression in the eosinophils by using RNA interference and addition of the DDR1-blocking protein abolished these effects. We propose that DDR1 contributes to the eosinophil survival in the tissue microenvironment of CSS and that it might be involved in the development of CSS.

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Section: Western Blot Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Discoidin domain receptor 1 contributes to eosinophil survival in an NF-κB–dependent manner in Churg-Strauss syndrome

Matsuyama

Mitsuyama

Ono

et al. 2006

Blood

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“…Fibroblasts cultured from IPF lungs possess a heritable profibrotic phenotype characterized by myofibroblastic differentiation (29) and increased collagen-1 (COL1) synthesis (36). Although epigenetic alterations are known to contribute (8,39), mechanisms driving the heritable profibrotic phenotype of IPF lung fibroblasts are poorly known.…”

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confidence: 99%

Forkhead Box F1 represses cell growth and inhibits COL1 and ARPC2 expression in lung fibroblasts in vitro

Melboucy‐Belkhir

Pradère

Tadbiri

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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Aberrant expression of master phenotype regulators or alterations in their downstream pathways in lung fibroblasts may play a central role in idiopathic pulmonary fibrosis (IPF). Interrogating IPF fibroblast transcriptome datasets, we identified Forkhead Box F1 (FOXF1), a DNA-binding protein required for lung development, as a candidate actor in IPF. Thus we determined FOXF1 expression levels in fibroblasts cultured from normal or IPF lungs in vitro, and explored FOXF1 functions in these cells using transient and stable loss-of-function and gain-of-function models. FOXF1 mRNA and protein were expressed at higher levels in IPF fibroblasts compared with normal fibroblasts (mRNA: ϩ44%, protein: ϩ77%). Immunohistochemistry showed FOXF1 expression in nuclei of bronchial smooth muscle cells, endothelial cells, and lung fibroblasts including fibroblastic foci of IPF lungs. In normal lung fibroblasts, FOXF1 repressed cell growth and expression of collagen-1 (COL1) and actin-related protein 2/3 complex, subunit 2 (ARPC2). ARPC2 knockdown inhibited cell growth and COL1 expression, consistent with FOXF1 acting in part through ARPC2 repression. In IPF fibroblasts, COL1 and ARPC2 repression by FOXF1 was blunted, and FOXF1 did not repress growth. FOXF1 expression was induced by the antifibrotic mediator prostaglandin E 2 and repressed by the profibrotic cytokine transforming growth factor-␤1 in both normal and IPF lung fibroblasts. Ex vivo, FOXF1 knockdown conferred CCL-210 lung fibroblasts the ability to implant in uninjured mouse lungs. In conclusion, FOXF1 functions and regulation were consistent with participation in antifibrotic pathways. Alterations of pathways downstream of FOXF1 may participate to fibrogenesis in IPF fibroblasts.

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“…Recent attention has focused on ECM components and mesenchymal cell phenotypes as being critical to the development of fibrosis (1,2). The ECM is a highly dynamic complex that varies in composition according to its tissue localization and physiologic circumstances.…”

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confidence: 99%

An Essential Role for Fibronectin Extra Type III Domain A in Pulmonary Fibrosis

Muro¹,

Moretti²,

Moore³

et al. 2008

Am J Respir Crit Care Med

265

254

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Rationale: Tissue fibrosis is considered a dysregulated wound-healing response. Fibronectin containing extra type III domain A (EDA) is implicated in the regulation of wound healing. EDA-containing fibronectin is deposited during wound repair, and its presence precedes that of collagen. Objectives: To investigate the role of EDA-containing fibronectin in lung fibrogenesis. Methods: Primary lung fibroblasts from patients with idiopathic pulmonary fibrosis or from patients undergoing resection for lung cancer were assessed for EDA-containing fibronectin and a-smooth muscle actin (a-SMA) expression. Mice lacking the EDA domain of fibronectin and their wild-type littermates were challenged with the bleomycin model of lung fibrosis. Primary lung fibroblasts from these mice were assayed in vitro to determine the contribution of EDA-containing fibronectin to fibroblast phenotypes. Measurements and Main Results: Idiopathic pulmonary fibrosis lung fibroblasts produced markedly more EDA-containing fibronectin and a-SMA than control fibroblasts. EDA-null mice failed to develop significant fibrosis 21 days after bleomycin challenge, whereas wildtype controls developed the expected increase in total lung collagen. Histologic analysis of EDA-null lungs after bleomycin showed less collagen and fewer a-SMA-expressing myofibroblasts compared with that observed in wild-type mice. Failure to develop lung fibrosis in EDA-null mice correlated with diminished activation of latent transforming growth factor (TGF)-b and decreased lung fibroblast responsiveness to active TGF-b in vitro. Conclusions: The data show that EDA-containing fibronectin is essential for the fibrotic resolution of lung injury through TGF-b activation and responsiveness, and suggest that EDA-containing fibronectin plays a critical role in tissue fibrogenesis.Keywords: fibrosis; fibronectin; TGF-b; myofibroblast Fibroproliferative disorders, characterized by the increased production and deposition of extracellular matrix (ECM) proteins in tissues, are not well understood despite major efforts to elucidate pathogenic mechanisms. Recent attention has focused on ECM components and mesenchymal cell phenotypes as being critical to the development of fibrosis (1, 2). The ECM is a highly dynamic complex that varies in composition according to its tissue localization and physiologic circumstances. Collagens are the predominant ECM proteins identified in fibrotic lesions and are the hallmark of fibroproliferative diseases, but fibronectins (FNs) are also present in abnormally large quantities and localize to areas of active fibrogenesis (3, 4).FNs are multifunctional glycoproteins found in the ECM of tissues and plasma. Two main forms of FN exist: plasma FN, a dimeric and soluble form produced by hepatocytes that lacks the EDA and EDB sequences, and cellular FN (cFN), a multimeric form synthesized by mesenchymal, epithelial, and inflammatory cells, which is deposited in ECM fibrils and that contains variable proportions of the extra type III domains A and B (EDA and EDB) (5...

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RETRACTED: Discoidin Domain Receptor 1 Contributes to the Survival of Lung Fibroblast in Idiopathic Pulmonary Fibrosis

Cited by 23 publications

References 49 publications

Discoidin domain receptor 1 contributes to eosinophil survival in an NF-κB–dependent manner in Churg-Strauss syndrome

Discoidin domain receptor 1 contributes to eosinophil survival in an NF-κB–dependent manner in Churg-Strauss syndrome

Forkhead Box F1 represses cell growth and inhibits COL1 and ARPC2 expression in lung fibroblasts in vitro

An Essential Role for Fibronectin Extra Type III Domain A in Pulmonary Fibrosis

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