Expression of bone morphogenetic protein 7 and its potential role in diabetic rats

Objective To observe the expression of bone morphogenetic protein 7 (BMP-7) in different stages of diabetic rats and investigate the potential role of BMP-7 in diabetic nephropathy (DN). Methods Wistar rats were divided into diabetes mellitus(DM) group induced by intravenous injection of streptozotocin (65 mg/kg) , and normal control group injected with citrate buffer. The rats were sacrificed at day 30,60,90,120,150 and 180 following injection, respectively. The blood glucose,Scr, urinary albumin and urinary creatinine were measured in each rat before sacrifice. The renal pathological changes were examined with hematoxylin and eosin (HE),periodic acid-silver-methenamine staining (PASM) and protein expression of collagenⅣ(ColⅣ). The mRNA and protein expression of BMP-7 and TGF-β1 in kidney were detected by reverse transcription-polymerase chain reaction (RT-RCR) and immunohistochemical staining respectively, and were quantified by computer image analysis system. Results The levels of blood glucose and urinary albumin in diabetic group were remarkably higher than those in control group (P 0.01). With the aggravation of diabetic nephropathy and increasing expression of ColⅣ, the expression of mRNA and protein of BMP-7 was progressively down-regulated (A%,30 d 95.87±1.19; 180 d 26.43±1.26)(P 0.01 or P 0.05), whereas the expression of TGF-β1 mRNA (A% 30 d 40.26±0.98; 180 d 102.12±6.45) and protein was significantly up-regulated in the diabetic rats as compared with that of the controls (A%,30 d 98.64±0.80;180 d 98.80±0.49)(P 0.01). The protein and mRNAlevels of BMP-7 were negatively correlated with TGF-β1 respectively (P 0.01). Conclusions Endogenous BMP-7 may be an important molecule for maintenance of renal homeostasis. The decrease of BMP-7 protein and mRNA during the early phase of diabetic nephropathy is possibly involved in the occurrence of diabetic nephropathy. BMP-7 may counteract TGF-β1-mediated profibrotic effects.