Abstract
The study investigated the expression of Wnt/β-catenin pathway in diabetic rats and the intervention effect of Huayu Tongluo herbs (HTH). Ten rats were randomly selected as control group and the remaining rats were established as diabetic models. The diabetic rats were randomly divided into model group and HTH treatment group. The intervention was intragastric administration in all rats for 20 weeks. At the end of every 4 weeks, fasting blood glucose and 24 h urinary total protein quantitatively were measured. At the end of the 20th week, biochemical parameters and body weight were tested. The kidney tissues were observed under light microscope and transmission electron microscopy. We examined Wnt/beta-catenin signaling pathway key proteins and renal interstitial fibrosis related molecular markers expression. The results showed that HTH could reduce urinary protein excretion and relieve renal pathological damage. Wnt4, p-GSK3β (S9), and β-catenin expression were decreased in the signaling pathway, but GSK3β level was not changed by HTH in diabetic rats. Furthermore, the expressions of TGF-β1 and ILK were decreased, but the level of E-cadherin was increased in diabetic rats after treatment with HTH. This study demonstrated that HTH could inhibit the high expression of Wnt/β-catenin pathway in kidney of diabetic rats. The effect might be one of the main ways to reduce urinary protein excretion.
Highlights
In the past three decades, diabetes patients were obviously increased with the improvement of life conditions in China
Studies reported that abnormal activation of Wnt/β-catenin signaling pathway mediating the podocyte injury in diabetic nephropathy caused a reduction in nephrin protein in the slit diaphragm, proliferation of mesangial cells, and renal interstitial fibrosis and proteinuria continued increasing
Based on the pathogenesis of blood stasis blocking collaterals in Diabetic nephropathy (DN), we demonstrated that Huayu Tongluo herbs (HTH) could reduce the loss of nephrin, podocin, CD2AP, and other proteins in podocyte slit diaphragm, protect podocytes, reduce renal fibrosis, and reduce urinary protein leakage [10,11,12]
Summary
In the past three decades, diabetes patients were obviously increased with the improvement of life conditions in China. Diabetic nephropathy (DN), one of the most serious and common chronic microvascular complications of diabetes mellitus (DM), is characterized by progressive proteinuria and glomerulosclerosis with renal interstitial fibrosis. It is one of the major causes of end-stage renal disease (ESRD), which brings heavy burden to society and family. Impairment of filtration barrier and loss of slit diaphragm protein are important causes of proteinuria. Studies reported that abnormal activation of Wnt/β-catenin signaling pathway mediating the podocyte injury in diabetic nephropathy caused a reduction in nephrin protein in the slit diaphragm, proliferation of mesangial cells, and renal interstitial fibrosis and proteinuria continued increasing
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