Linked Life Data

17198875

Source:http://linkedlifedata.com/resource/pubmed/id/17198875

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-1-2
pubmed:abstractText
Myelofibrosis is characterized by excessive deposits of extracellular matrix proteins, which occur as a marrow microenvironment reactive response to cytokines released from the clonal malignant myeloproliferation. The observation that mice exposed to high systemic levels of thrombopoietin (TPO) invariably developing myelofibrosis has allowed demonstration of the crucial role of transforming growth factor (TGF)-beta1 released by hematopoietic cells in the onset of myelofibrosis. The purpose of this study was to investigate whether TGF-beta1 inhibition could directly inhibit fibrosis development in a curative approach of this mice model. An adenovirus encoding for TGF-beta1 soluble receptor (TGF-beta-RII-Fc) was injected either shortly after transplantation (preventive) or 30 days post-transplantation (curative). Mice were transplanted with syngenic bone marrow cells transduced with a retrovirus encoding for murine TPO. All mice developed a myeloproliferative syndrome. TGF-beta-RII-Fc was detected in the blood of all treated mice, leading to a dramatic decrease in TGF-beta1 level. Histological analysis show that the two approaches (curative or preventive) were successful enough to inhibit bone marrow and spleen fibrosis development in this model. However, lethality of TPO overexpression was not decreased after treatment, indicating that in this mice model, myeloproliferation rather than fibrosis was probably responsible for the lethality induced by the disorder.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0301-472X
pubmed:author
pubmed:issnType
Print
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
64-74
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:17198875-Adenoviridae, pubmed-meshheading:17198875-Animals, pubmed-meshheading:17198875-Bone Marrow Cells, pubmed-meshheading:17198875-Bone Marrow Transplantation, pubmed-meshheading:17198875-Disease Models, Animal, pubmed-meshheading:17198875-Gene Therapy, pubmed-meshheading:17198875-Mice, pubmed-meshheading:17198875-Mice, SCID, pubmed-meshheading:17198875-Primary Myelofibrosis, pubmed-meshheading:17198875-Protein-Serine-Threonine Kinases, pubmed-meshheading:17198875-Receptors, Transforming Growth Factor beta, pubmed-meshheading:17198875-Splenic Diseases, pubmed-meshheading:17198875-Survival Analysis, pubmed-meshheading:17198875-Thrombopoietin, pubmed-meshheading:17198875-Transduction, Genetic, pubmed-meshheading:17198875-Transforming Growth Factor beta1, pubmed-meshheading:17198875-Transplantation, Isogeneic
pubmed:year
2007
pubmed:articleTitle
Adenoviral-mediated TGF-beta1 inhibition in a mouse model of myelofibrosis inhibit bone marrow fibrosis development.
pubmed:affiliation
INSERM U790, Pavillon de recherche 1, Institut Gustave Roussy, Villejuif Cedex, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't