Abstract:
RATIONALE:Activins are members of the transforming growth factor-beta superfamily thought to be involved in repair processes after tissue injury. OBJECTIVES:The aim of this study was to clarify whether activin and its antagonist, follistatin, played a significant role in lung injury and fibrosis. METHODS AND RESULTS:In bleomycin (BLM)-treated rat lung, mRNA for the beta(A) subunit of activin was upregulated on Days 3 and 7 and decreased gradually thereafter. Immunoreactive activin A was abundantly expressed in macrophages infiltrated in the lung, and was detected in fibroblasts accumulated in the fibrotic area on Day 28. We then administered follistatin, an activin antagonist, to BLM-treated rats. Follistatin significantly reduced the number of macrophages and neutrophils in bronchoalveolar lavage and reduced the protein content. Histologically, follistatin markedly reduced the number of infiltrating cells, ameliorated the destruction of lung architecture on Day 7, and attenuated lung fibrosis on Day 28. The hydroxyproline content was significantly lower in follistatin-treated rats. In cultured lung fibroblasts, production of activin A was augmented by transforming growth factor-beta, and activin antagonist follistatin significantly inhibited transforming growth factor-beta-induced fibroblast activation. These results suggest that activin A was produced in the lung after BLM treatment and promoted acute inflammation and subsequent fibrosis. CONCLUSIONS:Follistatin is effective in treating acute lung injury and BLM-induced fibrosis by blocking the actions of activin and transforming growth factor-beta.
journal_name
Am J Respir Crit Care Medauthors
Aoki F,Kurabayashi M,Hasegawa Y,Kojima Idoi
10.1164/rccm.200412-1620OCkeywords:
subject
Has Abstractpub_date
2005-09-15 00:00:00pages
713-20issue
6eissn
1073-449Xissn
1535-4970pii
200412-1620OCjournal_volume
172pub_type
杂志文章abstract:RATIONALE:Asthma is a chronic inflammatory airway disease that affects more than 300 million individuals worldwide. Asthma is caused by interaction of genetic and environmental factors. Bronchial hyperresponsiveness (BHR) is a hallmark of asthma and results from increased sensitivity of the airways to physical or chemi...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200810-1621OC
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abstract::Within the last few years, increasing evidence of relative adrenal insufficiency in septic shock evoked a reassessment of hydrocortisone therapy. To evaluate the effects of hydrocortisone on the balance between proinflammatory and antiinflammation, 40 patients with septic shock were randomized in a double-blind crosso...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
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abstract::The period covered by this update can be considered as the most exciting period in idiopathic pulmonary fibrosis (IPF) research. It started with the identification of genetic variants that are associated with IPF in the majority of patients and continued with discovery of molecular and genetic biomarkers that predict ...
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journal_title:American journal of respiratory and critical care medicine
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更新日期:2005-10-15 00:00:00
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journal_title:American journal of respiratory and critical care medicine
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更新日期:1998-07-01 00:00:00
abstract::The predisposing factors and complications of unplanned extubation (UEX) in mechanically ventilated adult patients are not well recognized. We designed a prospective multicenter observational study to identify risk factors and describe the complications of UEX. We followed 426 ventilated patients over a 2-mo period. C...
journal_title:American journal of respiratory and critical care medicine
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更新日期:1998-04-01 00:00:00
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abstract::To determine whether the cytokine interleukin (IL)-1 beta directly affects airway smooth muscle functions and, if so, what the mechanism of action is, we studied canine isolated bronchial segments under isometric conditions in vitro. Incubation of tissues with human recombinant IL-1 beta (10 ng/ml) for 150 min decreas...
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journal_title:American journal of respiratory and critical care medicine
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更新日期:2012-09-01 00:00:00
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journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:American journal of respiratory and critical care medicine
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journal_title:American journal of respiratory and critical care medicine
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journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,多中心研究
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更新日期:2009-10-01 00:00:00
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journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2000-07-01 00:00:00
abstract:RATIONALE:Cystic fibrosis (CF) is characterized by dietary antioxidant deficiencies, which may contribute to an oxidant-antioxidant imbalance and oxidative stress. OBJECTIVES:Evaluate the effects of an oral antioxidant-enriched multivitamin supplement on antioxidant concentrations, markers of inflammation and oxidativ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2018-09-01 00:00:00
abstract:RATIONALE:S. aureus is the most common respiratory pathogen isolated from patients with cystic fibrosis (CF) in the US. While modes of acquisition and genetic adaptation have been described for Pseudomonas aeruginosa, resulting in improved diagnosis and treatment, these features remain more poorly defined for S. aureus...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
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更新日期:2020-12-09 00:00:00
abstract::The rise in childhood asthma prevalence suggests a role for environmental factors in the etiology of this evolving epidemic; however, genetics also influence the occurrence of asthma. Glutathione S-transferase (GST) M1 may play a role in asthma and wheezing occurrence among those exposed to tobacco smoke, as it functi...
journal_title:American journal of respiratory and critical care medicine
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更新日期:2002-08-15 00:00:00
abstract::Thyroid transcription factor-1 (TTF-1) deficiency syndrome is characterized by neurologic, thyroidal, and pulmonary dysfunction. Children usually have mild-to-severe respiratory symptoms and occasionally die of respiratory failure. Herein, we describe an infant with a constitutional 14q12-21.3 haploid deletion encompa...
journal_title:American journal of respiratory and critical care medicine
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abstract::The interleukin-1 cluster on human chromosome 2q12-2q14 harbors various promising candidate genes for asthma and other inflammatory diseases. We conducted a systematic association study with single-nucleotide polymorphisms (SNPs) located in candidate genes situated in this cluster. Single-marker, two-locus and three-l...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:American journal of respiratory and critical care medicine
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更新日期:2013-04-01 00:00:00
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journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200705-742OC
更新日期:2008-02-01 00:00:00
abstract::Lymphocyte migration from the blood into the lung has been suggested as being responsible for the increase of lymphocytes, in particular CD4 T cells, in the bronchoalveolar lavage (BAL) and bronchial mucosa in human asthma, but so far there has been no direct proof. We studied lymphocyte immigration and lymphocyte sub...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
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更新日期:2000-02-01 00:00:00
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journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章
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更新日期:2008-07-15 00:00:00
abstract::Because inflammation stimulates the expression of inducible nitric oxide (NO) synthase (iNOS) with an associated increased local NO production, we hypothesized that patients with pneumonia would have increased excretion of NO into their airways. To test this hypothesis, NO was measured in the exhaled air and from the ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
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更新日期:2001-04-01 00:00:00
abstract::Although sleep-disordered breathing (SDB) has been shown to be very prevalent in the elderly, little has been done to examine differences between the elderly of different racial groups. It has been well documented that SDB often results in hypertension and that hypertension is more common in African-Americans than in ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
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abstract::The effects of conventional mechanical ventilation (CMV) and high-frequency oscillatory ventilation (HFO) on intraalveolar expression of the tumor necrosis factor-alpha (TNF-alpha) gene were studied in surfactant-depleted rabbits. After lung lavage with saline, 13 rabbits were administered either CMV (n = 6) or HFO (n...
journal_title:American journal of respiratory and critical care medicine
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更新日期:1997-07-01 00:00:00
abstract:RATIONALE:Nitric oxide (NO), synthesized by NOSs (NO synthases), plays a role in the development of pulmonary hypertension (PH). However, the role of NO/NOSs in bone marrow (BM) cells in PH remains elusive. OBJECTIVES:To determine the role of NOSs in BM cells in PH. METHODS:Experiments were performed on 36 patients w...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201709-1783OC
更新日期:2018-07-15 00:00:00
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journal_title:American journal of respiratory and critical care medicine
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更新日期:2018-03-01 00:00:00
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journal_title:American journal of respiratory and critical care medicine
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更新日期:1996-02-01 00:00:00
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journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.164.1.9911066
更新日期:2001-07-01 00:00:00