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

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.