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Volume 59, Issue 2, Pages 498-506 (February 2001)
Effect of anti-transforming growth factor-βbgr; antibodies in cyclosporine-induced renal dysfunction Muhammad Islam, James F. Burke, Tracy A. McGowan, Yanqing Zhu, Stephen R. Dunn, Peter McCue, John Kanalas, Kumar Sharma Kidney International Volume 59, Issue 2, Pages (February 2001) DOI: /j x Copyright © 2001 International Society of Nephrology Terms and Conditions
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Figure 1 Renal function is decreased with cyclosporine A (CsA) and attenuated by α-transforming growth factor-βbgr; (α-TGF-βbgr;) antibodies. Creatinine clearance was measured by 24-hour urine collections in all three groups. Creatinine clearance was reduced by 36% with CsA, whereas α-TGF-βbgr; treatment only had 13% reduction as compared with control. N = 9 per group, *P < vs. control, **P < 0.02 vs. CsA. Kidney International , DOI: ( /j x) Copyright © 2001 International Society of Nephrology Terms and Conditions
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Figure 2 Arteriolar hyalinosis from CsA is attenuated by α-TGF-βbgr;. Representative histologic sections from normal rat kidney (A), CsA-treated rat kidney (B), and CsA/α-TGF-βbgr;–treated rat kidney (C). As noted, there is arteriolar hyalinosis of the glomerular arteriole in the CsA-treated rat (arrow), whereas this lesion was significantly attenuated with α-TGF-βbgr; treatment. Periodic acid-Schiff–stained sections from formalin-fixed, paraffin-embedded tissue are shown. Kidney International , DOI: ( /j x) Copyright © 2001 International Society of Nephrology Terms and Conditions
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Figure 3 CsA-induced up-regulation of α1(I) collagen and TGF-βbgr;1 mRNA is significantly reduced by α-TGF-βbgr; treatment. (A) Representative Northern analysis of α1(I) collagen (upper panel), TGF-βbgr;1 (middle panel), and βbgr;-actin (lower panel) mRNA expression in kidneys from control rats, CsA-treated rats, and CsA/α-TGF-βbgr; treated rats. Quantitative analysis from all samples tested (N = 7 per group) demonstrated a significant increase in the ratio of α1(I) collagen/βbgr;-actin (B) and TGF-βbgr;1/βbgr;-actin mRNA expression (C) as compared with the control group. Treatment with α-TGF-βbgr; antibodies completely normalized α1(I) collagen expression and attenuated the increase in TGF-βbgr;1 mRNA expression. *P < 0.05 vs. control; **P < 0.05 vs. CsA. Kidney International , DOI: ( /j x) Copyright © 2001 International Society of Nephrology Terms and Conditions
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Figure 4 CsA-induced down-regulation of matrix metalloprotein-9 (MMP-9) is partially prevented by α-TGF-βbgr; treatment. Quantitative RT-PCR results for MMP-2 and MMP-9 in CsA-treated rats and CsA/α-TGF-βbgr; rats expressed as percentage of control (N = 7 per group). There is a significant increase in MMP-2 mRNA expression in the CsA group, but there is no effect of α-TGF-βbgr; treatment. In contrast, there is a marked reduction of MMP-9 mRNA expression (15% of control value, P < 0.001), and there is a significant, but partial, prevention with α-TGF-βbgr; treatment (44% of control). *P < 0.02 vs. control. **P < 0.02 vs. CsA. Kidney International , DOI: ( /j x) Copyright © 2001 International Society of Nephrology Terms and Conditions
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Figure 5 α-TGF-βbgr; treatment significantly attenuates the increased expression of TIMP-1, but not PAI-1, induced by CsA. Quantitative RT-PCR results of TIMP-1, TIMP-2, and PAI-1 in CsA and CsA/α-TGF-βbgr; group as compared with control values. TIMP-1 expression is increased by over 7.4-fold in CsA-treated rats but only to 4.2-fold in CsA rats treated with α-TGF-βbgr;. There is no effect on TIMP-2 expression with CsA. PAI-1 is increased by twofold with CsA, but not significantly attenuated with α-TGF-βbgr; treatment. *P < 0.02 vs. control. **P < vs. CsA. Kidney International , DOI: ( /j x) Copyright © 2001 International Society of Nephrology Terms and Conditions
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