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


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.


CONCLUSIONS
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.
Department of Molecular Medicine & Genetics, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
Maryam Foroutan
MF
Jazi
Cancer Gene Therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.
Alireza
A
Biglari
Department of Epidemiology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
Saeideh
S
Mazloomzadeh
Vascular Gene Therapy Unit, Research School of Clinical & Laboratory Sciences, Manchester Academic Health Science Center, The University of Manchester, Manchester, UK.
Paul
P
Kingston
Cancer Gene Therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.
Ali
A
Ramazani
Department of Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Javad Tavkoli
JT
Bazzaz
Department of Physiology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
Mehdi
M
Eskandari
Diabetic nephropathy; Diabetic rats; Fibromodulin; Gene therapy; TGF-β1