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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2011-5-20
pubmed:abstractText
Neonatal respiratory distress syndrome can progress to bronchopulmonary dysplasia (BPD), a serious pulmonary fibrotic disorder. Given the involvement of the extrinsic coagulation cascade in animal models of lung fibrosis, we examined its role in BPD. We observed a higher number of neutrophils expressing tissue factor (TF) in bronchoalveolar lavage fluid (BALF) from infants with BPD than from those with uncomplicated respiratory distress syndrome together with a parallel decrease in TF and connective tissue growth factor (CTGF) in BALF supernatants during the disease course. The involvement of coagulation in the fibrotic process associated with BPD was further evaluated by treating primary human colonic myofibroblasts with BALF supernatants from infants with BPD. These human colonic myofibroblasts demonstrated an enhanced C5a- and thrombin-dependent migration. Moreover, they expressed TF in an endothelin-1-dependent manner, with subsequent activation of the extrinsic coagulation cascade and CTGF production mediated by protease-activator receptor-1 signaling. These data provide a novel mechanism for the development of BPD and indicate that endothelin-1 signaling contributes to fibrosis by upregulating a TF/thrombin amplification loop responsible for CTGF production, and offer novel and specific therapeutic targets for pulmonary fibrotic disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
186
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6568-75
pubmed:meshHeading
pubmed-meshheading:21531894-Blotting, Western, pubmed-meshheading:21531894-Bronchoalveolar Lavage Fluid, pubmed-meshheading:21531894-Bronchopulmonary Dysplasia, pubmed-meshheading:21531894-Cells, Cultured, pubmed-meshheading:21531894-Colon, pubmed-meshheading:21531894-Complement C5a, pubmed-meshheading:21531894-Connective Tissue Growth Factor, pubmed-meshheading:21531894-Endothelin-1, pubmed-meshheading:21531894-Female, pubmed-meshheading:21531894-Fibrosis, pubmed-meshheading:21531894-Green Fluorescent Proteins, pubmed-meshheading:21531894-Humans, pubmed-meshheading:21531894-Immunohistochemistry, pubmed-meshheading:21531894-Infant, Newborn, pubmed-meshheading:21531894-Lung, pubmed-meshheading:21531894-Male, pubmed-meshheading:21531894-Microscopy, Fluorescence, pubmed-meshheading:21531894-Myofibroblasts, pubmed-meshheading:21531894-Receptor, PAR-1, pubmed-meshheading:21531894-Receptors, Complement, pubmed-meshheading:21531894-Respiratory Distress Syndrome, Newborn, pubmed-meshheading:21531894-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:21531894-Signal Transduction, pubmed-meshheading:21531894-Thrombin, pubmed-meshheading:21531894-Thromboplastin
pubmed:year
2011
pubmed:articleTitle
Endothelin-1 signaling promotes fibrosis in vitro in a bronchopulmonary dysplasia model by activating the extrinsic coagulation cascade.
pubmed:affiliation
First Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis 68100, Greece.
pubmed:publicationType
Journal Article