Alleviation by Mahuang Fuzi and Shenzhuo Decoction in High Glucose-Induced Podocyte Injury by Inhibiting the Activation of Wnt/β-Catenin Signaling Pathway, Resulting in Activation of Podocyte Autophagy.

Haoran Dai,Qihan Zhao,Xuefei Tian,Zihan Zhang,Zhaocheng Dong,Chang Gao,Yingmin Jia,Zhiyuan Liu,Yu Gao,Baoli Liu,Zhendong Feng,Wenbin Liu,Fei Liu,Xinping Qiu,Songge Sun

doi:10.1155/2020/7809427

Abstract

Background Organ fibrosis is a common endpoint of a variety of diseases. Many studies have shown that the pathogenesis of diabetic kidney disease (DKD) is related to the excessive activation of the Wnt/β-catenin signaling pathway on podocytes, so the treatment of DKD starts from this signaling pathway. At the same time, DKD, as a metabolic disease, has many connections related to podocyte autophagy. Objectives We experimented the effects of Mahuang Fuzi and Shenzhuo decoction (MFSD) which is the combination of Mahuang Fuzi decoction and Shenzhuo decoction in traditional Chinese medicine compounds used “The Golden Chamber” in high glucose-induced podocytes, determined whether this effect was related to Wnt/β-catenin signaling pathway, and further investigated the relationship between this effect and autophagy. Methods The mice podocytes were stimulated by using 30 mmol/L of high glucose and serum containing MFSD or Wnt/β-catenin signaling pathway inhibitor DKK1 (100 ng/ml) was used to intervene podocytes before high glucose stimulation. Podocyte injury-related proteins, Wnt/β-catenin signaling pathway-related proteins, and autophagy-related proteins were detected by using western blotting and immunofluorescence analysis. Results Our results showed that DKK1 and MFSD treatment significantly upregulated the protein expressions of nephrin, podocin, podocalyxin, and podoplanin in high glucose-induced podocytes and downregulated the β-catenin protein expression. Furthermore, the protein expressions of beclin1, LC3B, and P62 were also significantly increased in high glucose-induced podocytes. Conclusion Our experiments confirmed that the destruction of podocytes in DKD is related to the excessive activation of Wnt/β-catenin signaling pathway and the inhibition of autophagy after activation. MFSD treatment can inhibit the activation of Wnt/β-catenin signaling pathway in podocytes stimulated by high glucose and helpful in reducing the podocyte injury. This protective mechanism can be related to the enhancement of podocyte autophagy by MFSD treatment.

Highlights

Diabetic kidney disease (DKD) is one of the major complications of diabetes [1]. e traditional therapies of diabetic kidney disease (DKD) are mostly based on hypoglycemic, antihypertensive, diet, and lifestyle [2]
We observed the morphology of the Mahuang Fuzi and Shenzhuo decoction (MFSD) group after a 24hour intervention under light microscopy (Figure 1). e cells were differentiated after being cultured at 37°C in an incubator with 5% CO2 for 10 days to 14 days, the adherent growth area of the cells increases significantly, and a large number of secondary protrusions protrude from the main part of the cell body, making cells to appear “dendritic” or “flower-like.” ere is no obvious difference in morphology between the two groups of podocytes. is shows that the MFSD-containing serum has no obvious effect on the morphology of podocytes
We found out that the expression levels of nephrin and podocin were significantly decreased in high glucose conditions

Summary

Introduction

Diabetic kidney disease (DKD) is one of the major complications of diabetes [1]. e traditional therapies of DKD are mostly based on hypoglycemic, antihypertensive, diet, and lifestyle [2]. Extensive studies have shown that autophagy was regulated by a variety of mechanisms, including activation of the Wnt/β-catenin signaling pathway [20, 21]. Many studies have shown that the pathogenesis of diabetic kidney disease (DKD) is related to the excessive activation of the Wnt/β-catenin signaling pathway on podocytes, so the treatment of DKD starts from this signaling pathway. Our experiments confirmed that the destruction of podocytes in DKD is related to the excessive activation of Wnt/β-catenin signaling pathway and the inhibition of autophagy after activation. MFSD treatment can inhibit the activation of Wnt/β-catenin signaling pathway in podocytes stimulated by high glucose and helpful in reducing the podocyte injury. MFSD treatment can inhibit the activation of Wnt/β-catenin signaling pathway in podocytes stimulated by high glucose and helpful in reducing the podocyte injury. is protective mechanism can be related to the enhancement of podocyte autophagy by MFSD treatment

Objectives

Methods

Results

Discussion

Conclusion