The role of bmp-7 and tgf-ß1 in diabetic nephropathy

الملخص EN

-Diabetic nephropathy (DN) is a common complication of diabetes mellitus which has a major impact on patient morbidity and mortality.

It is now the commonest cause of renal failure requiring renal replacement therapy worldwide.

Factors that promote diabetic nephropathy include sustained hyperglycemia, genetic susceptibility, systemic hypertension, dyslipidemia and growth factors.

There are profibrotic growth factors such as transforming growth factor-beta 1 (TGF-ß1) and antifibrotic growth factors such as bone morphogenic protein-7(BMP-7).

Bone morphogenic protein-7 is a glycosylated disulphide-linked 36 kDa homodimeric protein.

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It is expressed primarily in the kidney tubules.

BMP-7 is the main antifibrotic growth factor that has been proven experimentally to protect against development of DN in diabetic rats.

Transforming growth factor-beta1(TGF- ß1) a 25 kD polypeptide, the profibrotic TGF- ? 1 is involved in the development of renal scarring through increased synthesis and decreased degradation of extracellular matrix (ECM) components, as well as to the activation of myofibroblasts in the tubulointerstitial area.

Aim:The present work aimed at estimation of serum levels of bone morphogenic protein-7 (BMP-7) and transforming growth factor-? 1 (TGF- ß1) in relation to kidney function; glomerular filtration rate and urinary albumin in type 2 diabetic males.

Subjects:The present study was conducted on sixty adult males divided into two main groups.

The control group included fifteen apparently healthy male volunteers.

The patients group included forty five diabetic male patients.

These patients were further sorted into 3 subgroups according to their urinary albumin creatinine ratio.

Methods:To all studied subjects; thorough history taking, physical examination and laboratory investigations which included : complete urine analysis with quantitative determination of urine albumin, creatinine and urine/creatinine ratio, estimation of serum levels of glucose (fasting and 2 hours postprandial), creatinine, uric acid, triglycerides, total cholesterol and C-reactive protein (CRP) levels.

Also aminotranferases (AST&ALT) and alkaline phosphatase activities, glycated hemoglobin (HBA1C) as well as calculation of the glomerular filtration rate ,estimation of plasma thiobarbituric acid reactive substances (TBARS), serum levels of bone morphogenic protein-7 (BMP-7), and transforming growth factor-beta 1 (TGF--ß1) were done.

Conclusions:The following could be concluded from the obtained results: - The significant decrease in the BMP-7 levels especially in the macroalbuminuric patients verifies the renoprotective role of BMP-7.

- The significant increase in the TGF-? 1 levels especially in the macroalbuminuric patients and the strong negative correlation with the BMP-7 confirms the contribution of both BMP-7 and TGF-? 1 in the progression of diabetic nephropathy.