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

Foroutan Jazi, Maryam and Biglari, Alireza and Mazloomzadeh, Saeideh and Kingston, Paul and Ramazani, Ali and Tavkoli Bazzaz, Javad and Eskandari, Mehdi (2016) Recombinant fibromodulin has therapeutic effects on diabetic nephropathy by down-regulating transforming growth factor-β1 in streptozotocin-induced diabetic rat model. Iranian Journal of Basic Medical Sciences, 19 (3). pp. 265-271.

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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.

Item Type: Article
Subjects: QT physiology
Divisions: Journals > Iranian J Basic Medical Sciences
Depositing User: ijbms ijbms
Date Deposited: 29 Sep 2017 00:18
Last Modified: 29 Sep 2017 00:18
URI: http://eprints.mums.ac.ir/id/eprint/6573

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