Recombinant fibromodulin has therapeutic effects on diabetic nephropathy by down-regulating transforming growth factor-β1 in streptozotocin-induced diabetic rat model

重组纤维调节蛋白通过下调链脲佐菌素诱发的糖尿病大鼠模型中的转化生长因子-β1对糖尿病肾病具有治疗作用

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作者:Maryam Foroutan Jazi, Alireza Biglari, Saeideh Mazloomzadeh, Paul Kingston, Ali Ramazani, Javad Tavkoli Bazzaz, Mehdi Eskandari

Conclusion

Intraperitoneal injection of adenoviral vectors expressing fibromodulin reduced TGF-β1 level in diabetic rat models. The molecular mechanisms involved in this process require further study.

Methods

Forty-eight Sprague-Dawley rats were divided into 4 groups: STZ-induced diabetic rats (diabetic-control), fibromodulin adenovirus vector treated STZ rats (Ad- fibromodulin), and Ad-lacZ-treated STZ rats (Ad-lacZ), and vehicle control (PBS-control). At 10 weeks after STZ treatment, we measured urinary albumin excretion (UAE), urine creatinine was measured by Jaffe method. We also measured kidney TGF-β1 levels by reverse transcription polymerase chain reaction and Real-time PCR.

Results

Urine albumin to creatinine ratio or UAE level were listed in four groups. UAE difference between healthy and diabetic rats in all three groups were significant (P≤0.005) and between the control group and treated groups were not significant. Our results indicated that TGF-β1gene expression in diabetic rats were increased and difference between normal group and diabetic group were significant (P≤0.001). Fibromodulin gene transfection mediated by a recombinant adenovirus decreased TGF-β1 level in STZ-induced diabetic rats and TGF-β1 mRNA in diabetic kidney were reduced 2 weeks after Ad-fibromodulin injection.

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