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[Effect of bone morphogenic protein 7 on nephrin expression and distribution in diabetic rat kidneys]
Hou-qin Xiao1, Wei Shi, Yong Zhang
1Department of Nephrology, Guangdong Provincial People's Hospital, Southern Medical University, Guangzhou 510080, China. xhq7301 @tom.com
Objective:
To evaluate the effect of bone morphogenic protein 7 (BMP-7) on nephrin expression and distribution in diabetic rat kidneys.
Methods:
Twenty rats with diabetes mellitus (DM) induced by streptozotocin (STZ) injection were randomly divided into DM model group and BMP-7 treatment group, with another 10 normal rats serving as the normal control group. The rats in BMP-7 group received intraperitoneal human recombinant BMP-7 injections at 30 microg/kg twice a week for 24 consecutive weeks, while normal saline was administered in rats of the other two groups. Blood glucose and 24 hour urinary protein and creatinine (Ccr) were measured at 8, 16 and 24 weeks, and the rats were sacrificed at 24 weeks to obtain the renal tissues for detecting the expression and distribution of nephrin using immunofluorescence assay and RT-PCR and for examining the expressions of transforming growth factor-beta1 (TGF-beta1) and WT1 using immunohistochemistry.
Results:
Compared with the normal control group, the DM model group showed significantly increased 24 hour urinary protein, kidney to body weight ratio and TGF-beta1 expression, but had lowered Ccr, glomerular podocyte number and nephrin expression. The linear distribution of nephrin along the capillary loops as found in the normal control group became granular in the kidney of diabetic rats. The rats in BMP-7 group showed less urinary protein excretion, lower TGF-beta1 expression and greater glomerular podocyte number than those in the DM group, and the expression and distribution of nephrin remained normal in the kidney.
Conclusion:
Administration of BMP-7 can significantly suppress the down-regulation of nephrin expression and maintain its normal distribution in the podocytes in diabetic rats possibly in association with a direct suppression of TGF-betasignaling.
Insights
Bone morphogenic protein 7 (BMP-7) treatment maintained normal nephrin expression and distribution in diabetic rat kidneys. BMP-7 suppressed down-regulation of nephrin, potentially by inhibiting TGF-beta signaling.
Area of Science:
- Nephrology
- Endocrinology
- Molecular Biology
Context:
- Diabetic nephropathy is a major complication of diabetes mellitus.
- Nephrin is a crucial podocyte protein essential for glomerular filtration barrier integrity.
- Diabetic kidney disease is characterized by progressive loss of podocyte function and nephrin expression.
Purpose:
- To investigate the therapeutic potential of bone morphogenic protein 7 (BMP-7) in preserving nephrin expression and distribution in a rat model of diabetic nephropathy.
- To evaluate the impact of BMP-7 on key markers of kidney injury, including urinary protein, creatinine clearance, and transforming growth factor-beta1 (TGF-beta1) signaling.
Summary:
- Administration of human recombinant BMP-7 to streptozotocin-induced diabetic rats for 24 weeks mitigated kidney damage.
- BMP-7 treatment preserved nephrin expression and its linear distribution along capillary loops, unlike in untreated diabetic rats where it became granular.
- BMP-7 significantly reduced urinary protein excretion, lowered TGF-beta1 expression, and maintained glomerular podocyte numbers compared to the diabetic model group.
Impact:
- BMP-7 demonstrates a protective effect against diabetic nephropathy by maintaining podocyte integrity and glomerular filtration.
- This study suggests BMP-7 as a potential therapeutic agent for diabetic kidney disease, possibly through direct suppression of TGF-beta signaling.
- Understanding BMP-7's role in nephrin regulation offers insights into novel treatment strategies for diabetic kidney complications.
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