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פותח על ידי קלירמאש פתרונות בע"מ -
Inhibition of rat renal fibroblast proliferation by halofuginone
Year:
2006
Source of publication :
Nephron - Experimental Nephrology
Authors :
פינס, מרק
;
.
Volume :
104
Co-Authors:
Haran, N., Department of Nephrology and Hypertension, Kaplan Medical Center, Rehovot, Israel
Leschinski, L., Department of Nephrology and Hypertension, Kaplan Medical Center, Rehovot, Israel
Pines, M., Volcani Institute, Bet Dagan, Israel
Rapoport, J., Department of Nephrology and Hypertension, Kaplan Medical Center, Rehovot, Israel, Faculty of Medicine, Hebrew University, Jerusalem, Israel, Department of Nephrology and Hypertension, Kaplan Medical Center, POB 1, Rehovot 76100, Israel
Facilitators :
From page:
To page:
(
Total pages:
1
)
Abstract:
Background/Aim: Interstitial fibrosis is the final common pathway of renal damage and represents an important therapeutic target. Halofuginone is a nontoxic alkaloid, used as a coccidiostat, and is a potent inhibitor of collagen α1(I) and matrix metalloproteinase-2 (MMP-2) expression. We thus studied the effects of halofuginone on proliferation, collagen I synthesis, and MMP-2 activity of rat renal papillary fibroblasts in culture. Methods: Fibroblasts were isolated from rat renal papillae and studied during passages 3-4. The cell proliferation was studied in the presence of varying concentrations of halofuginone. The collagen synthesis was studied by [ 3H]proline uptake, before and after collagenase digestion, at varying concentrations of halofuginone. The MMP-2 activity was determined by zymography. The gelatinolytic activity was determined on gelatin-impregnated polyacrylamide gels containing samples of cell medium after incubation for 24 h with different halofuginone doses. Results: We studied a phenotype of papillary fibroblasts which stained positive for alpha smooth muscle actin. These cells are phenotypically myofibroblasts. Halufuginone inhibited the proliferation of these cells in a dose-related and reversible manner. Platelet-derived growth factor is known to stimulate fibroblast proliferation. Halofuginone at a concentration of 250 ng/ml almost completely abolished the effect of platelet-derived growth factor. It also almost completely inhibited the MMP-2 activity at doses of 250-350 ng/ml, as shown by zymography. Conclusions: Halofuginone exhibits antifibrotic effects in rat renal papillary fibroblasts in culture, in terms of inhibition of proliferation and inhibition of MMP-2. These findings could have therapeutic potential. Copyright © 2006 S. Karger AG.
Note:
Related Files :
animal cell
Animals
Cell Proliferation
kidney papilla
Male
phenotype
tritium
zymography
עוד תגיות
תוכן קשור
More details
DOI :
10.1159/000093674
Article number:
Affiliations:
Database:
סקופוס
Publication Type:
מאמר
;
.
Language:
אנגלית
Editors' remarks:
ID:
25717
Last updated date:
02/03/2022 17:27
Creation date:
17/04/2018 00:17
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Scientific Publication
Inhibition of rat renal fibroblast proliferation by halofuginone
104
Haran, N., Department of Nephrology and Hypertension, Kaplan Medical Center, Rehovot, Israel
Leschinski, L., Department of Nephrology and Hypertension, Kaplan Medical Center, Rehovot, Israel
Pines, M., Volcani Institute, Bet Dagan, Israel
Rapoport, J., Department of Nephrology and Hypertension, Kaplan Medical Center, Rehovot, Israel, Faculty of Medicine, Hebrew University, Jerusalem, Israel, Department of Nephrology and Hypertension, Kaplan Medical Center, POB 1, Rehovot 76100, Israel
Inhibition of rat renal fibroblast proliferation by halofuginone
Background/Aim: Interstitial fibrosis is the final common pathway of renal damage and represents an important therapeutic target. Halofuginone is a nontoxic alkaloid, used as a coccidiostat, and is a potent inhibitor of collagen α1(I) and matrix metalloproteinase-2 (MMP-2) expression. We thus studied the effects of halofuginone on proliferation, collagen I synthesis, and MMP-2 activity of rat renal papillary fibroblasts in culture. Methods: Fibroblasts were isolated from rat renal papillae and studied during passages 3-4. The cell proliferation was studied in the presence of varying concentrations of halofuginone. The collagen synthesis was studied by [ 3H]proline uptake, before and after collagenase digestion, at varying concentrations of halofuginone. The MMP-2 activity was determined by zymography. The gelatinolytic activity was determined on gelatin-impregnated polyacrylamide gels containing samples of cell medium after incubation for 24 h with different halofuginone doses. Results: We studied a phenotype of papillary fibroblasts which stained positive for alpha smooth muscle actin. These cells are phenotypically myofibroblasts. Halufuginone inhibited the proliferation of these cells in a dose-related and reversible manner. Platelet-derived growth factor is known to stimulate fibroblast proliferation. Halofuginone at a concentration of 250 ng/ml almost completely abolished the effect of platelet-derived growth factor. It also almost completely inhibited the MMP-2 activity at doses of 250-350 ng/ml, as shown by zymography. Conclusions: Halofuginone exhibits antifibrotic effects in rat renal papillary fibroblasts in culture, in terms of inhibition of proliferation and inhibition of MMP-2. These findings could have therapeutic potential. Copyright © 2006 S. Karger AG.
Scientific Publication
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