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פותח על ידי קלירמאש פתרונות בע"מ -
Gene expression during chemically induced liver fibrosis: Effect of halofuginone on TGF-β signaling
Year:
2007
Source of publication :
Cell and Tissue Research
Authors :
בילו, ג'
;
.
גנאינסקי, יוליה
;
.
גנין, אולגה
;
.
וולפין, חנה
;
.
חגי, יוסי
;
.
פינס, מרק
;
.
קושנירסקי, צביקה
;
.
Volume :
328
Co-Authors:
Gnainsky, Y., Institute of Animal Sciences, Volcani Center, P.O. Box 6, Bet Dagan 50250, Israel
Kushnirsky, Z., Genomics and Bioinformatics Center Agricultural Research Organization, Volcani Center, Bet Dagan, Israel
Bilu, G., Institute of Animal Sciences, Volcani Center, P.O. Box 6, Bet Dagan 50250, Israel
Hagai, Y., Institute of Animal Sciences, Volcani Center, P.O. Box 6, Bet Dagan 50250, Israel
Genina, O., Institute of Animal Sciences, Volcani Center, P.O. Box 6, Bet Dagan 50250, Israel
Volpin, H., Genomics and Bioinformatics Center Agricultural Research Organization, Volcani Center, Bet Dagan, Israel
Bruck, R., Department of Gastroenterology, Holon and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Spira, G., Department of Anatomy and Cell Biology, Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel
Nagler, A., Division of Hematology, Sheba Medical Center, Tel Hashomer, Israel
Kawada, N., Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan
Yoshizato, K., Department of Biological Science, Graduate School of Science, Hiroshima University, Hiroshima, Japan
Reinhardt, D.P., Department of Anatomy and Cell Biology, Faculties of Medicine and Dentistry, McGill University, Montreal, Que., Canada
Libermann, T.A., BIDMC Genomics Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
Pines, M., Institute of Animal Sciences, Volcani Center, P.O. Box 6, Bet Dagan 50250, Israel
Facilitators :
From page:
153
To page:
166
(
Total pages:
14
)
Abstract:
Hepatic fibrosis is associated with the activation of stellate cells (HSCs), the major source of extracellular matrix (ECM) proteins. Transforming growth factor-β (TGF-β), signaling via Smad3, is the most profibrogenic cytokine and the major promoter of ECM synthesis. Halofuginone, an inhibitor of liver fibrosis, inhibits TGF-β-dependent Smad3 phosphorylation in human HSCs in culture. We have used transcriptional profiling to evaluate the effect of halofuginone on gene expression during the progression of thioacetamide (TAA)-induced liver fibrosis in the rat and have focused on genes that are associated with TGF-β. TAA treatment causes alterations in the expression of 7% of liver genes. Halofuginone treatment prevents the changes in the expression of 41% of these genes and results in the inhibition of HSC activation and collagen synthesis. During the early stages of the disease, halofuginone affects genes involved in alcohol, lipid, protein, and phosphate metabolism and cell adhesion and, at later stages, in the cell cycle (cell development, differentiation, cell proliferation, and apoptosis). The activation of TGF-β-dependent genes, such as tartrate-resistant acid phosphatase, its putative substrate osteopontin, stellate cell activation-association protein, and fibrillin-1, during chemically induced fibrosis is prevented by halofuginone. This study thus highlights the role of TGF-β signaling in liver fibrosis and especially its potential for pharmacological intervention. Halofuginone, which has demonstrated efficacy and tolerance in animals and humans, could become an effective and novel therapy for liver fibrosis. © 2006 Springer-Verlag.
Note:
Related Files :
animal experiment
Animals
apoptosis
Cell Proliferation
gene expression
Male
transforming growth factor beta
עוד תגיות
תוכן קשור
More details
DOI :
10.1007/s00441-006-0330-1
Article number:
0
Affiliations:
Database:
סקופוס
Publication Type:
מאמר
;
.
Language:
אנגלית
Editors' remarks:
ID:
24098
Last updated date:
02/03/2022 17:27
Creation date:
17/04/2018 00:05
You may also be interested in
Scientific Publication
Gene expression during chemically induced liver fibrosis: Effect of halofuginone on TGF-β signaling
328
Gnainsky, Y., Institute of Animal Sciences, Volcani Center, P.O. Box 6, Bet Dagan 50250, Israel
Kushnirsky, Z., Genomics and Bioinformatics Center Agricultural Research Organization, Volcani Center, Bet Dagan, Israel
Bilu, G., Institute of Animal Sciences, Volcani Center, P.O. Box 6, Bet Dagan 50250, Israel
Hagai, Y., Institute of Animal Sciences, Volcani Center, P.O. Box 6, Bet Dagan 50250, Israel
Genina, O., Institute of Animal Sciences, Volcani Center, P.O. Box 6, Bet Dagan 50250, Israel
Volpin, H., Genomics and Bioinformatics Center Agricultural Research Organization, Volcani Center, Bet Dagan, Israel
Bruck, R., Department of Gastroenterology, Holon and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Spira, G., Department of Anatomy and Cell Biology, Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel
Nagler, A., Division of Hematology, Sheba Medical Center, Tel Hashomer, Israel
Kawada, N., Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan
Yoshizato, K., Department of Biological Science, Graduate School of Science, Hiroshima University, Hiroshima, Japan
Reinhardt, D.P., Department of Anatomy and Cell Biology, Faculties of Medicine and Dentistry, McGill University, Montreal, Que., Canada
Libermann, T.A., BIDMC Genomics Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
Pines, M., Institute of Animal Sciences, Volcani Center, P.O. Box 6, Bet Dagan 50250, Israel
Gene expression during chemically induced liver fibrosis: Effect of halofuginone on TGF-β signaling
Hepatic fibrosis is associated with the activation of stellate cells (HSCs), the major source of extracellular matrix (ECM) proteins. Transforming growth factor-β (TGF-β), signaling via Smad3, is the most profibrogenic cytokine and the major promoter of ECM synthesis. Halofuginone, an inhibitor of liver fibrosis, inhibits TGF-β-dependent Smad3 phosphorylation in human HSCs in culture. We have used transcriptional profiling to evaluate the effect of halofuginone on gene expression during the progression of thioacetamide (TAA)-induced liver fibrosis in the rat and have focused on genes that are associated with TGF-β. TAA treatment causes alterations in the expression of 7% of liver genes. Halofuginone treatment prevents the changes in the expression of 41% of these genes and results in the inhibition of HSC activation and collagen synthesis. During the early stages of the disease, halofuginone affects genes involved in alcohol, lipid, protein, and phosphate metabolism and cell adhesion and, at later stages, in the cell cycle (cell development, differentiation, cell proliferation, and apoptosis). The activation of TGF-β-dependent genes, such as tartrate-resistant acid phosphatase, its putative substrate osteopontin, stellate cell activation-association protein, and fibrillin-1, during chemically induced fibrosis is prevented by halofuginone. This study thus highlights the role of TGF-β signaling in liver fibrosis and especially its potential for pharmacological intervention. Halofuginone, which has demonstrated efficacy and tolerance in animals and humans, could become an effective and novel therapy for liver fibrosis. © 2006 Springer-Verlag.
Scientific Publication
You may also be interested in