Hepatocyte growth factor in bronchoalveolar lavage fluids and cells in patients with inflammatory chest diseases of the lower respiratory tract: detection by RIA and in situ hybridization.

Sakai, Toshihiko; Satoh, Ken; Matsushima, Kisa; Shindo, Satoshi; Abe, Shigefusa; Abé, Tatsuya; Motomiya, Masakichi; Kawamoto, T.; Kawabata, Yoshinori; Nakamura, Toshikazu; Nukiwa, Toshihiro

doi:10.1165/ajrcmb.16.4.9115749

Cited by 44 publications

(39 citation statements)

References 37 publications

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“…HGF is known to have an anti-apoptotic effect on epithelial cells, enhance apoptosis in myofibroblasts [41] and is involved in the local regulation of fibrinolysis and coagulation [42]. Clinically, levels of HGF have been found to be elevated in both serum [43] and bronchoalveolar lavage fluid [44] of patients with either IPF or collagen vascular disease-associated pulmonary fibrosis. In the BLM-induced lung injury mouse model, administration of HGF reduces fibrosis and morphological changes [45].…”

Section: Therapeutic Manipulation Of Apoptosismentioning

confidence: 99%

The role of apoptosis in pulmonary fibrosis

Uhal¹

2008

Eur Respir Rev

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Apoptosis has been defined as ''gene-directed cellular self-destruction'' and is an active process that is tightly regulated by a number of gene products, which promote or block cell death. Apoptotic death can be triggered by a wide variety of stimuli and, importantly, not all cells necessarily undergo apoptosis in response to the same stimulus. Abnormal regulation of apoptosis has been implicated in a wide range of diseases and approaches to modifying apoptosis represent important future therapeutic strategies.Idiopathic pulmonary fibrosis (IPF) is a progressive and relentless disease involving scarring of the lung, which has been recognised as the most lethal interstitial lung disease. In the lungs of IPF patients, increased epithelial apoptosis, together with decreased apoptosis of myofibroblasts, represents persistent findings (particularly in areas of collagen deposition) supporting an interaction between altered apoptosis and the pathogenesis of the disease.Data from human tissues and animal models are refining current knowledge of the processes involved in this pathogenesis. This has challenged the dogma that IPF is purely a disease of unresolved inflammation by emphasising the central roles played by the alveolar epithelial cell and myofibroblasts and, as part of that role, the importance of altered apoptosis.Evidence suggests blockade of epithelial cell apoptosis can prevent subsequent collagen deposition, and induction of myofibroblast apoptosis, at least theoretically, would be expected to resolve ongoing fibrosis. These two concepts raise the prospect of therapeutic intervention aimed at modifying apoptosis and, thus, fibrosis in idiopathic pulmonary fibrosis.

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Section: Therapeutic Manipulation Of Apoptosismentioning

confidence: 99%

The role of apoptosis in pulmonary fibrosis

Uhal¹

2008

Eur Respir Rev

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“…HGF levels are increased in the BAL fluid of patients with idiopathic pulmonary fibrosis, sarcoidosis, and the interstitial lung disease associated with rheumatoid arthritis. 18 HGF is also up-regulated following bleomycin administration in normal mice. 19 When administered systemically or intratracheally, HGF has been shown to attenuate pulmonary fibrosis following bleomycin-induced injury in mice.…”

mentioning

confidence: 96%

The Plasminogen Activation System Reduces Fibrosis in the Lung by a Hepatocyte Growth Factor-Dependent Mechanism

Hattori

Mizuno

Yoshida

et al. 2004

The American Journal of Pathology

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Mice deficient in the plasminogen activator inhibitor-1 gene (PAI-1؊/؊ mice) are relatively protected from developing pulmonary fibrosis from bleomycin administration. We hypothesized that one of the protective mechanisms may be the ability of the plasminogen system to enhance hepatocyte growth factor (HGF) effects, which have been reported to be antifibrotic in the lung. HGF is known to be sequestered in tissues by binding to extracellular matrix components. Following bleomycin administration, we found that HGF protein levels were higher in bronchoalveolar lavage fluid from PAI-1 ؊/؊ mice com- Abnormal accumulation of fibrin occurs within the interstitium and alveolar spaces of the lung in a variety of pulmonary diseases in which the integrity of the capillary alveolar barrier is damaged.

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“…P ulmonary fibrosis is an inflammatory interstitial lung disease characterised by an accumulation of alveolar macrophages and neutrophils in the lower respiratory tract, alveolar epithelial injury, and aberrant alveolar wound repair [1,2]. Previous studies have indicated that efficient alveolar epithelial cell repair is critical for normal healing without fibrosis [3][4][5].…”

mentioning

confidence: 99%

Apoptotic cell instillation after bleomycin attenuates lung injury through hepatocyte growth factor induction

Lee

Moon²,

Lee³

et al. 2012

Eur Respir J

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Apoptotic cell clearance by macrophages and neighbouring tissue cells induces hepatocyte growth factor (HGF) secretion. HGF plays a key role in alveolar epithelial regeneration and reconstruction after lung injury. Direct in vivo exposure to apoptotic cells enhances HGF production, resulting in attenuation of pulmonary injury.We investigated the direct effect of in vivo exposure to apoptotic cells in bleomycin-stimulated lungs (2 days old) on HGF induction. Furthermore, sequential changes of bleomycin-induced HGF production following apoptotic cell instillation related to the changes in inflammatory and fibrotic responses were assessed.At 2 h after apoptotic cell instillation into bleomycin-stimulated lungs, the levels of HGF mRNA and protein production, and apoptotic cell clearance by alveolar macrophages were enhanced. Furthermore, HGF induction persistently increased following apoptotic cell instillation up to 21 days after bleomycin treatment. Apoptotic cell instillation attenuated bleomycin-induced proinflammatory mediator production, inflammatory cell recruitment and total protein levels. Apoptotic cell instillation also induced antiapoptotic and antifibrotic effects. These antiinflammatory and antiapoptotic effects could be reversed by co-administration of HGFneutralising antibody.These findings indicate that in vivo exposure to apoptotic cells enhances transcriptional HGF production in bleomycin-stimulated lungs, resulting in attenuation of lung injury and fibrosis.

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Hepatocyte growth factor in bronchoalveolar lavage fluids and cells in patients with inflammatory chest diseases of the lower respiratory tract: detection by RIA and in situ hybridization.

Cited by 44 publications

References 37 publications

The role of apoptosis in pulmonary fibrosis

The role of apoptosis in pulmonary fibrosis

The Plasminogen Activation System Reduces Fibrosis in the Lung by a Hepatocyte Growth Factor-Dependent Mechanism

Apoptotic cell instillation after bleomycin attenuates lung injury through hepatocyte growth factor induction

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