Abstract
Background: We recently demonstrated that upregulation of the transforming growth factor (TGF)-β1 inducible gene-h3 (ßig-h3) is associated with tubulointerstitial fibrosis (TIF) in a rat model of chronic cyclosporine A (CsA) nephrotoxicity. This study investigated the association between ßig-h3 expression and TIF during losartan treatment in this model. Methods: Adult Sprague-Dawley rats kept on a salt-depleted diet (0.05% sodium) were treated daily for 4 weeks with vehicle (olive oil, 1 ml/kg), CsA (15 mg/kg) or both CsA and losartan (10 mg/kg in drinking water). The effect of losartan on ßig-h3 expression was evaluated using in situ hybridization, immunohistochemistry and immunoblotting. Histopathology, expressions of TGF-ß1 and intrarenal angiotensin II were compared across treatment groups. Results: Concurrent administration of losartan significantly attenuated ßig-h3 mRNA and protein expression within the tubulointerstitium of CsA-treated kidneys. This was accompanied by the retardation of TIF (18 ± 5 vs. 39 ± 5%, p < 0.01 vs. CsA) and the expression of TGF-β1 mRNA (336 ± 49 vs. 685 ± 63%, p < 0.01 vs. CsA) and the number of angiotensin II-positive glomeruli (18 ± 5 vs. 38 ± 6, p < 0.05 vs. CsA). Conclusion: Losartan is capable of abrogating the upregulation of TGF-β1 and ßig-h3 expression, and this is associated with attenuated tubulointerstitial fibrosis in chronic CsA nephrotoxicity.
| Original language | English |
|---|---|
| Journal | Nephron - Experimental Nephrology |
| Volume | 99 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2005 Feb 3 |
| Externally published | Yes |
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Keywords
- Cyclosporine
- Extracellular matrix
- Fibrosis
- Losartan
- Renin angiotensin system
- TGF-β1-inducible gene-h3
- Transforming growth factor-β1
ASJC Scopus subject areas
- Physiology
- Genetics
- Nephrology
Cite this
Blockade of angiotensin II with losartan attenuates transforming growth factor-β1 inducible gene-h3 (ßig-h3) expression in a model of chronic cyclosporine nephrotoxicity. / Sun, Bo Kyung; Li, Can; Lim, Sun Woo; Choi, Bum Soon; Lee, Suk Hee; Kim, In-San; Kim, Yong Soo; Bang, Byung Kee; Yang, Chul Woo.
In: Nephron - Experimental Nephrology, Vol. 99, No. 1, 03.02.2005.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Blockade of angiotensin II with losartan attenuates transforming growth factor-β1 inducible gene-h3 (ßig-h3) expression in a model of chronic cyclosporine nephrotoxicity
AU - Sun, Bo Kyung
AU - Li, Can
AU - Lim, Sun Woo
AU - Choi, Bum Soon
AU - Lee, Suk Hee
AU - Kim, In-San
AU - Kim, Yong Soo
AU - Bang, Byung Kee
AU - Yang, Chul Woo
PY - 2005/2/3
Y1 - 2005/2/3
N2 - Background: We recently demonstrated that upregulation of the transforming growth factor (TGF)-β1 inducible gene-h3 (ßig-h3) is associated with tubulointerstitial fibrosis (TIF) in a rat model of chronic cyclosporine A (CsA) nephrotoxicity. This study investigated the association between ßig-h3 expression and TIF during losartan treatment in this model. Methods: Adult Sprague-Dawley rats kept on a salt-depleted diet (0.05% sodium) were treated daily for 4 weeks with vehicle (olive oil, 1 ml/kg), CsA (15 mg/kg) or both CsA and losartan (10 mg/kg in drinking water). The effect of losartan on ßig-h3 expression was evaluated using in situ hybridization, immunohistochemistry and immunoblotting. Histopathology, expressions of TGF-ß1 and intrarenal angiotensin II were compared across treatment groups. Results: Concurrent administration of losartan significantly attenuated ßig-h3 mRNA and protein expression within the tubulointerstitium of CsA-treated kidneys. This was accompanied by the retardation of TIF (18 ± 5 vs. 39 ± 5%, p < 0.01 vs. CsA) and the expression of TGF-β1 mRNA (336 ± 49 vs. 685 ± 63%, p < 0.01 vs. CsA) and the number of angiotensin II-positive glomeruli (18 ± 5 vs. 38 ± 6, p < 0.05 vs. CsA). Conclusion: Losartan is capable of abrogating the upregulation of TGF-β1 and ßig-h3 expression, and this is associated with attenuated tubulointerstitial fibrosis in chronic CsA nephrotoxicity.
AB - Background: We recently demonstrated that upregulation of the transforming growth factor (TGF)-β1 inducible gene-h3 (ßig-h3) is associated with tubulointerstitial fibrosis (TIF) in a rat model of chronic cyclosporine A (CsA) nephrotoxicity. This study investigated the association between ßig-h3 expression and TIF during losartan treatment in this model. Methods: Adult Sprague-Dawley rats kept on a salt-depleted diet (0.05% sodium) were treated daily for 4 weeks with vehicle (olive oil, 1 ml/kg), CsA (15 mg/kg) or both CsA and losartan (10 mg/kg in drinking water). The effect of losartan on ßig-h3 expression was evaluated using in situ hybridization, immunohistochemistry and immunoblotting. Histopathology, expressions of TGF-ß1 and intrarenal angiotensin II were compared across treatment groups. Results: Concurrent administration of losartan significantly attenuated ßig-h3 mRNA and protein expression within the tubulointerstitium of CsA-treated kidneys. This was accompanied by the retardation of TIF (18 ± 5 vs. 39 ± 5%, p < 0.01 vs. CsA) and the expression of TGF-β1 mRNA (336 ± 49 vs. 685 ± 63%, p < 0.01 vs. CsA) and the number of angiotensin II-positive glomeruli (18 ± 5 vs. 38 ± 6, p < 0.05 vs. CsA). Conclusion: Losartan is capable of abrogating the upregulation of TGF-β1 and ßig-h3 expression, and this is associated with attenuated tubulointerstitial fibrosis in chronic CsA nephrotoxicity.
KW - Cyclosporine
KW - Extracellular matrix
KW - Fibrosis
KW - Losartan
KW - Renin angiotensin system
KW - TGF-β1-inducible gene-h3
KW - Transforming growth factor-β1
UR - http://www.scopus.com/inward/record.url?scp=12444292702&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=12444292702&partnerID=8YFLogxK
U2 - 10.1159/000081793
DO - 10.1159/000081793
M3 - Article
C2 - 15637465
AN - SCOPUS:12444292702
VL - 99
JO - Experimental Nephrology
JF - Experimental Nephrology
SN - 0028-2766
IS - 1
ER -