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[Effects of rosiglitazone on the expression connective tissue growth factor in tubulointerstitium in KKA(y) mice]
Yan Qin1, Xue-wang Li, Yu-bing Wen
1Department of Nephrology, PUMC Hospital, CAMS and PUMC, Beijing 100730, China.
Objective:
To observe the expression of connective tissue growth factor (CTGF) in the tubulointerstitium in type 2 diabetic KKA(y) mice and the effect of rosiglitazone on it.
Methods:
KKA(y) and C57 BL/6 mice aged 16 weeks ( n = 5 in each group) were sacrificed as controls before treatment. Another 20 KKA(y) mice were treated with rosiglitazone (30 mg x kg (-1) d (-1), n = 10) or placebo (n = 10). The mice were sacrificed at 20 and 24-week-age (n = 5 at each time point). Protein expression of transforming growth factor-beta1 (TGF-beta1 ), CTGF, peroxisome proliferator-activated receptor-gamma (PPARgamma) , and fibronectin were assayed by Western blot, while protein CTGF, PPARgamma, and alpha-smooth muscle actin ( alpha-SMA) were assayed by immunohistochemistry in kidney tissue sections.
Results:
Proteinuria was significantly decreased in mice aged 24 weeks treated by rosiglitazone than same-aged mice treated with placebo [ (44. 53+/-1. 96) vs (63. 66 +/-5. 57) microg/24 h, P < 0. 05 ]. The expressions of TGF-beta1, CTGF, and fibronectin in mice aged 20 weeks treated with rosiglitazone decreased by 37% , 21% , and 52% than same-aged control (P <0. 01) , and those were decreased by 61% , 50% , and 51% in mice aged 24 weeks treated with rosiglitazone compared with same-aged control mice (P < 0. 01). CTGF in the tubulointerstitium were respectively downregulated by 25% and 44. 9% in treated mice aged 20 weeks and 24 weeks compared with the same-aged control mice ( P < 0. 01). The PPARgamma appeared in diabetic mice and increased by 18. 1% in mice aged 24 weeks and treated with rosiglitazone than the same-aged control mice (P <0. 05).
Conclusion:
Heterogeneous rosiglitazone may upregulate the expression of PPARgamma in renal cortex, and remarkably inhibit the expressions of CTGF in the tubulointerstitium and renal cortex in diabetic KKA(y) mice.
Insights
Rosiglitazone treatment significantly reduced proteinuria and inhibited connective tissue growth factor (CTGF) expression in the kidneys of type 2 diabetic mice. This suggests a potential therapeutic benefit of rosiglitazone in diabetic nephropathy.
Area of Science:
- Nephrology
- Endocrinology
- Pharmacology
Background:
- Diabetic nephropathy is a major complication of type 2 diabetes.
- Connective tissue growth factor (CTGF) plays a critical role in the pathogenesis of renal fibrosis.
- Understanding the molecular mechanisms underlying diabetic kidney disease is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the expression of CTGF in the tubulointerstitium of type 2 diabetic KKA(y) mice.
- To evaluate the effect of rosiglitazone on CTGF expression and related markers in diabetic kidneys.
Main Methods:
- Type 2 diabetic KKA(y) mice and control C57 BL/6 mice were used.
- Mice were treated with rosiglitazone or placebo.
- Kidney tissues were analyzed for protein expression of TGF-beta1, CTGF, fibronectin, PPARgamma, and alpha-SMA using Western blot and immunohistochemistry.
Main Results:
- Rosiglitazone treatment significantly reduced proteinuria in 24-week-old diabetic mice.
- Expressions of TGF-beta1, CTGF, and fibronectin were significantly decreased by rosiglitazone in both 20- and 24-week-old mice.
- CTGF expression in the tubulointerstitium was downregulated by rosiglitazone.
- PPARgamma expression was upregulated by rosiglitazone in the renal cortex.
Conclusions:
- Rosiglitazone may upregulate PPARgamma expression in the renal cortex.
- Rosiglitazone remarkably inhibits CTGF expression in the tubulointerstitium and renal cortex of diabetic mice.
- These findings suggest a potential renoprotective role for rosiglitazone in type 2 diabetes.
