Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-7-22
pubmed:abstractText
Hepatic fibrinogen (FBG) is upregulated during an acute phase response (APR) induced by glucocorticoids and interleukin (IL)-6. Furthermore, intestine and lung epithelium synthesize FBG after exposure to inflammatory mediators, and both plasma and lung cell-derived FBG, along with fibronectin, assemble in detergent-insoluble extracellular matrices (ECM) of pneumocytes and fibroblasts independent of thrombin or plasmin cleavage. An epitope cryptic in soluble FBG (beta(15-21)) but exposed in matrix-FBG and fibrin induces cell proliferation and actin cytoskeleton reorganization during wound repair and angiogenesis. Although fibrin(ogen) is involved in hemostasis and homeostasis, mechanisms regulating extrahepatic FBG expression remain unexplored. Herein we examined FBG production by lung compared to liver epithelial cell lines in response to dexamethasone (DEX)+IL-6. Regulated synthesis of HepG2-FBG follows the pathway shown for constitutive synthesis by liver epithelium. Constitutive A549-FBG expression was not detectable, however, intracellular FBG precursors in DEX+IL-6-treated A549 lung cells were similar to HepG2 cells with two notable exceptions. The relative rate of chain synthesis in HepG2 cells was unequal, whereas nascent synthesis of all three chains occurred at equivalent rates in stimulated A549 cells. Unlike HepG2 cells, which rapidly secreted intact FBG, nascent dimeric FBG accumulated in the A549 cell-associated fraction prior to release into medium. Furthermore, soluble A549-FBG was susceptible to thrombin and plasmin cleavage. Interestingly, many functionally diverse proteins possess FBG-related domains that direct cell-fate determination during development or wound repair, suggesting that extrahepatic FBG biosynthesis evoked only during inflammation plays such a role during localized injury and repair to restore tissue homeostasis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0340-6245
pubmed:author
pubmed:issnType
Print
pubmed:volume
92
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
234-43
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15269818-Acute-Phase Reaction, pubmed-meshheading:15269818-Cell Line, pubmed-meshheading:15269818-Cell Line, Tumor, pubmed-meshheading:15269818-Cell Proliferation, pubmed-meshheading:15269818-Cells, Cultured, pubmed-meshheading:15269818-Cytoskeleton, pubmed-meshheading:15269818-Detergents, pubmed-meshheading:15269818-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:15269818-Epithelial Cells, pubmed-meshheading:15269818-Epithelium, pubmed-meshheading:15269818-Extracellular Matrix, pubmed-meshheading:15269818-Fibrinogen, pubmed-meshheading:15269818-Fibrinolysin, pubmed-meshheading:15269818-Glucocorticoids, pubmed-meshheading:15269818-Glycosylation, pubmed-meshheading:15269818-Homeostasis, pubmed-meshheading:15269818-Humans, pubmed-meshheading:15269818-Inflammation, pubmed-meshheading:15269818-Interleukin-6, pubmed-meshheading:15269818-Intestines, pubmed-meshheading:15269818-Liver, pubmed-meshheading:15269818-Lung, pubmed-meshheading:15269818-Thrombin, pubmed-meshheading:15269818-Time Factors, pubmed-meshheading:15269818-Up-Regulation, pubmed-meshheading:15269818-Wound Healing
pubmed:year
2004
pubmed:articleTitle
Regulated de novo biosynthesis of fibrinogen in extrahepatic epithelial cells in response to inflammation.
pubmed:affiliation
Department of Medicine-Hematology/Oncology Unit, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.