Variable Expression of Platelet-derived Growth Factor Family Proteins in Acute Lung Injury

Walsh, James J.; Absher, Marlene; Kelley, Jason

doi:10.1165/ajrcmb/9.6.637

Cited by 55 publications

(40 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…8,9,11,28 In rat models of fibrosis, PDGF and the PDGF ␣-receptor subtype are increased 2 to 3 days after lung injury by bleomycin or metals. 4,29 EGF and TGF-␣ are elevated 2 to 4 days in the rat bleomycin model. Asbestos fibers also stimulate the secretion of PDGF isoforms and TGF-␣ in vitro and in vivo in rodent models.…”

Section: Discussionmentioning

confidence: 92%

Specific Inhibitors of Platelet-Derived Growth Factor or Epidermal Growth Factor Receptor Tyrosine Kinase Reduce Pulmonary Fibrosis in Rats

Rice

Moomaw

Morgan

et al. 1999

The American Journal of Pathology

135

107

View full text Add to dashboard Cite

The proliferation of myofibroblasts is a central feature of pulmonary fibrosis. In this study we have used tyrosine kinase inhibitors of the tyrphostin class to specifically block autophosphorylation of the platelet-derived growth factor receptor (PDGF-R) or epidermal growth factor receptor (EGF-R). AG1296 specifically inhibited autophosphorylation of PDGF-R and blocked PDGF-stimulated [ 3 H]thymidine uptake by rat lung myofibroblasts in vitro. AG1478 was demonstrated as a selective blocker of EGF-R autophosphorylation and inhibited EGF-stimulated DNA synthesis in vitro. In a rat model of pulmonary fibrosis caused by intratracheal instillation of vanadium pentoxide (V 2 O 5 ) , intraperitoneal delivery of 50 mg/kg AG1296 or AG1478 in dimethylsulfoxide 1 hour before V 2 O 5 instillation and again 2 days after instillation reduced the number of epithelial and mesenchymal cells incorporating bromodeoxyuridine (Brdu) by ϳ50% at 3 and 6 days after instillation. V 2 O 5 instillation increased lung hydroxyproline fivefold 15 days after instillation , and AG1296 was more than 90% effective in preventing the increase in hydroxyproline , whereas AG1478 caused a 50% to 60% decrease in V 2 O 5 -stimulated hydroxyproline accumulation. These data provide evidence that PDGF and EGF receptor ligands are potent mitogens for collagen-producing mesenchymal cells during pulmonary fibrogenesis , and targeting tyrosine kinase receptors could offer a strategy for the treatment of fibrotic lung diseases. (Am J Pathol 1999, 155:213-221)

show abstract

Section: Discussionmentioning

confidence: 92%

Specific Inhibitors of Platelet-Derived Growth Factor or Epidermal Growth Factor Receptor Tyrosine Kinase Reduce Pulmonary Fibrosis in Rats

Rice

Moomaw

Morgan

et al. 1999

The American Journal of Pathology

135

107

View full text Add to dashboard Cite

show abstract

“…Animal models of acute lung injury and pulmonary fibrosis reveal increased expression of PDGF-B mRNA and PDGF-BB prior to deoxyribonucleic acid synthesis and tissue repair [11,26,27]. In addition, PDGF-BB has been shown to contribute to the fibroblast mitogenic activity of BAL fluid in bleomycin-induced pulmonary fibrosis [11].…”

Section: Discussionmentioning

confidence: 99%

“…Platelet-derived growth factor (PDGF)-BB is a potent mitogen for fibroblasts and increased pulmonary levels are associated with pulmonary fibrosis [4]. Additionally, PDGF-BB has been shown to contribute to BAL fluid-induced fibroblast proliferation in an animal model of bleomycininduced acute lung injury [11]. It has been reported that expression of PDGF-B messenger ribonucleic acid (mRNA) by alveolar macrophages, which are considered an important source of PDGF in the development of pulmonary fibrosis, is upregulated by DEX [12].…”

mentioning

confidence: 99%

Dexamethasone treatment does not inhibit fibroproliferation in chronic lung disease of prematurity

Dik¹,

Versnel²,

Naber³

et al. 2003

Eur Respir J

View full text Add to dashboard Cite

Pulmonary fibrosis results from excessive fibroblast proliferation and increased collagen deposition and occurs in chronic lung disease of prematurity (CLD). Platelet-derived growth factor (PDGF)-BB is mitogenic for fibroblasts and levels are increased in fibrotic lung disorders. Systemic dexamethasone (DEX) treatment improves pulmonary function and reduces inflammation in infants with or at risk of CLD. However, the effect of DEX treatment on fibroblast activity, PDGF-BB and collagen synthesis in the lungs of CLD patients is uncertain.Bronchoalveolar lavage (BAL) fluids, obtained from 15 infants at risk of CLD before and after DEX treatment, were analysed for fibroblast mitogenicity, PDGF-BB, N-terminal propeptide of collagen type III (PIIINP) and interleukin (IL)-1b levels and inflammatory cell numbers.After DEX treatment, the mitogenic activity of BAL fluid for fibroblasts was not reduced but increased. The change in mitogenicity correlated with a change in BAL fluid PDGF-BB levels. Furthermore, BAL fluid-induced fibroblast proliferation was blocked using an inhibitor of the PDGF receptor. DEX treatment did not influence PIIINP levels, but reduced IL-1b levels and inflammatory cell numbers in BAL fluid.This study suggests that dexamethasone treatment does not reduce fibroblast proliferation despite apparent downregulation of inflammation. The present findings do not support the use of dexamethasone for prevention of the fibrotic response in infants at risk of chronic lung disease of prematurity. Neonatal respiratory distress syndrome (RDS) is characterised by pulmonary inflammation with neutrophils and macrophages as the main cell types [1,2]. RDS can progress towards chronic lung disease (CLD) of prematurity, also known as bronchopulmonary dysplasia. Risk factors for the development of CLD include premature birth with concomitant lung immaturity, mechanical ventilator-induced lung injury, oxygen toxicity and pulmonary inflammation [3].Pulmonary fibrosis is characterised by excessive fibroblast proliferation and increased collagen deposition [4] and is a common feature in infants dying because of CLD [5]. Increased pulmonary levels of fibrogenic mediators, such as fibronectin and transforming growth factor-b 1 , which increase proliferation and collagen synthesis by fibroblasts, have been associated with CLD development [6,7].Treatment with systemic dexamethasone (DEX) is commonly used in infants with or at risk of CLD and improves pulmonary function, facilitates weaning from the ventilator and reduces pulmonary inflammation [8]. However, it has been suggested that DEX treatment may not inhibit the development of pulmonary fibrosis in CLD, since it does not decrease fibronectin concentrations in bronchoalveolar lavage (BAL) fluid [6]. Conversely, DEX treatment of CLD infants results in decreased urinary excretion of hydroxyproline, indicating suppressed collagen synthesis in these infants [9]. However, the specific effect of DEX treatment on lung collagen synthesis during CLD development remains unc...

show abstract

“…Importantly, we discovered that PDGF, which was more strongly expressed in INSIP. Intriguingly, some studies indicate that PDGF can promote the proliferation of fibroblasts (23). In bleomycininduced mice, PDGF was significantly increased in murine pulmonary tissues (24), and target its expression could availably prevent the progress of fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Lower expression of platelet derived growth factor is associated with better overall survival rate of patients with idiopathic nonspecific interstitial pneumonia

et al. 2017

View full text Add to dashboard Cite

Background: Idiopathic nonspecific interstitial pneumonia (INSIP) presents with varying degrees of interstitial inflammation and fibrosis exhibiting a uniform appearance. Lack of knowledge on the underlying mechanisms of INSIP has contributed to few effective treatment strategies. Our study is designed to explore aberrantly expressed cytokines involvement in INSIP development.Methods: Oligo GEArray was employed to detect the expression of cytokines in INSIP patients, and idiopathic pulmonary fibrosis (IPF) was setup as isotype control. Real-time PCR and immunohistochemistry analysis were used to further confirm the expression of abnormally expressed cytokines. The correlationship between cytokines expression and overall survival rate of patients with IPF and INSIP were analyzed.Results: From microarray detection, transforming growth factor-beta-1 (TGF-β1), fibroblast growth factor 10 (FGF10), and platelet derived growth factor (PDGF) were predominantly up-regulated in patients with INSIP. Real-time PCR and immunohistochemistry also showed these cytokines was abnormally expressed in INSIP. In addition to, the clinical relevance analysis demonstrated relatively lower expression of PDGF patients had longer overall survival rate than those with higher expression of PDGF.Conclusions: Our study suggests that TGF-β1, FGF10, and PDGF are required for the pathogenesis of INSIP, and may therefore be ideal targets in INSIP treatment. Moreover, INSIP patients with lower expression of PDGF had better survival rate.Keywords: Idiopathic nonspecific interstitial pneumonia (INSIP); idiopathic pulmonary fibrosis (IPF); transforming growth factor-beta-1 (TGF-β1); fibroblast growth factor 10 (FGF10); platelet derived growth factor (PDGF)

show abstract

Variable Expression of Platelet-derived Growth Factor Family Proteins in Acute Lung Injury

Cited by 55 publications

References 32 publications

Specific Inhibitors of Platelet-Derived Growth Factor or Epidermal Growth Factor Receptor Tyrosine Kinase Reduce Pulmonary Fibrosis in Rats

Specific Inhibitors of Platelet-Derived Growth Factor or Epidermal Growth Factor Receptor Tyrosine Kinase Reduce Pulmonary Fibrosis in Rats

Dexamethasone treatment does not inhibit fibroproliferation in chronic lung disease of prematurity

Lower expression of platelet derived growth factor is associated with better overall survival rate of patients with idiopathic nonspecific interstitial pneumonia

Contact Info

Product

Resources

About