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

Document Type: Original Article

Authors

1 Department of Molecular Medicine & Genetics, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran

2 Cancer Gene Therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran

3 Department of Epidemiology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran

4 Vascular Gene Therapy Unit, Research School of Clinical & Laboratory Sciences, Manchester Academic Health Science Center, The University of Manchester, Manchester, UK

5 Department of Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

6 Department of Physiology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran

Abstract

Objective(s):Diabetic nephropathy is an important long-term complication of diabetes mellitus which appears to be partially mediated by an increase in secretion of transforming growth factor-β (TGF-β). Fibromodulin, the small leucine-rich proteoglycan, has been proposed to be the potent TGFβ1 modulator. In this study, the therapeutic effects of recombinant adenoviral vectors expressing fibromodulin on TGF-β1 expression on diabetic nephropathy were assessed.
Materials and 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.
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.

Keywords


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