Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2005-9-12
pubmed:abstractText
The hyaluronan-binding protease (HABP) is a serine protease in human plasma which is structurally related to plasminogen activators, coagulation factor XII and hepathocyte growth factor activator. It can in vitro activate the coagulation factor FVII, kininogen and plasminogen activators. The present study was initiated to gain a more complete picture of the cell-associated activities of this fibrinolysis-related protease. Treatment of lung fibroblasts with HABP lead to a rapid activation of signalling pathways, including the mitogen-activated protein kinase (MAPK) pathway with c-Raf, MEK and ERK1/2. Additionally the activation of the PI3K/Akt pathway and of several translation-related proteins was found. Proliferation assays confirmed the assumption of a strong growth-stimulating effect of HABP on human lung and skin fibroblasts. Intracellular signalling and growth stimulation were strongly dependent on the proteolytic activity of HABP. Stimulation of signalling and proliferation by HABP involved the fibroblast growth factor receptor 1 (FGFR-1). HABP-stimulated proliferation of lung fibroblasts MRC-5 was accompanied by a significant intracellular increase in basic fibroblast growth factor (bFGF), the major ligand of FGFR-1; bFGF could however not be identified in the supernatant of HABP-treated cells. Though, the conditioned medium from HABP-treated cells showed a strong growth-promoting activity on quiescent fibroblasts, indicating the release of a yet unknown growth factor amplifying the initial growth stimulus. In a two-dimensional wound model HABP stimulated the invasion of fibroblasts into a scratch area, adding a strong pro-migratory activity to this plasma protease. In summary, HABP exhibits a significant growth factor-like activity on quiescent human lung and dermal fibroblasts. Our findings suggest that this fibrinolysis-related plasma protease may participate in physiologic or pathologic processes where cell proliferation and migration are pivotal, like tissue repair, vascular remodelling, wound healing or tumor development.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Androstadienes, http://linkedlifedata.com/resource/pubmed/chemical/Butadienes, http://linkedlifedata.com/resource/pubmed/chemical/Culture Media, Conditioned, http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 1, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3, http://linkedlifedata.com/resource/pubmed/chemical/Nitriles, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Pyrroles, http://linkedlifedata.com/resource/pubmed/chemical/SU 5402, http://linkedlifedata.com/resource/pubmed/chemical/Serine Endopeptidases, http://linkedlifedata.com/resource/pubmed/chemical/U 0126, http://linkedlifedata.com/resource/pubmed/chemical/hyaluronan-binding protease, human, http://linkedlifedata.com/resource/pubmed/chemical/wortmannin
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0898-6568
pubmed:author
pubmed:issnType
Print
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1486-94
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:16153533-Androstadienes, pubmed-meshheading:16153533-Butadienes, pubmed-meshheading:16153533-Cell Line, pubmed-meshheading:16153533-Cell Movement, pubmed-meshheading:16153533-Cell Proliferation, pubmed-meshheading:16153533-Culture Media, Conditioned, pubmed-meshheading:16153533-Fibroblasts, pubmed-meshheading:16153533-Humans, pubmed-meshheading:16153533-Lung, pubmed-meshheading:16153533-MAP Kinase Kinase 1, pubmed-meshheading:16153533-MAP Kinase Signaling System, pubmed-meshheading:16153533-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:16153533-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:16153533-Nitriles, pubmed-meshheading:16153533-Phosphatidylinositol 3-Kinases, pubmed-meshheading:16153533-Phosphorylation, pubmed-meshheading:16153533-Pyrroles, pubmed-meshheading:16153533-Serine Endopeptidases, pubmed-meshheading:16153533-Skin, pubmed-meshheading:16153533-Time Factors, pubmed-meshheading:16153533-Up-Regulation
pubmed:year
2005
pubmed:articleTitle
The hyaluronan-binding protease upregulates ERK1/2 and PI3K/Akt signalling pathways in fibroblasts and stimulates cell proliferation and migration.
pubmed:affiliation
Department of Hematology/Transfusion Medicine, Paul Ehrlich Institute, Federal Agency for Sera and Vaccines, Paul-Ehrlich-Strasse 51-59, 63225 Langen, Germany. etsmi@pei.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't