Panax Notoginseng Ameliorates Podocyte EMT by Targeting the Wnt/β-Catenin Signaling Pathway in STZ-Induced Diabetic Rats

Abstract

Introduction

Epithelial–mesenchymal transition (EMT) may contribute to podocyte dysfunction in diabetic nephropathy (DN). Aiming to identify novel therapeutic options, we investigated the protective effects of Panax notoginseng (PN) on podocyte EMT in diabetic rats and explored its mechanisms.

Methods

Diabetes was induced in rats with streptozotocin (STZ) by intraperitoneal injection at 55 mg/kg. Diabetic rats were randomly divided into three groups, namely, diabetic rats, diabetic rats treated with beraprost sodium (BPS) at 0.6 mg/kg/d or PN at 0.4 g/kg/d p.o., for 12 weeks. Urinary albumin/creatinine ratio (ACR), biochemical parameters, renal histopathology, and podocyte morphological changes were evaluated. Protein expression of EMT markers (desmin, α-SMA, and nephrin) as well as components of the Wnt/β-catenin pathway (wnt1, β-catenin, and snail) was detected by immunohistochemistry and Western blot, respectively.

Results

In diabetic rats, severe hyperglycemia and albuminuria were detected. Moreover, mesangial expansion and podocyte foot process effacement were found markedly increased in diabetic kidneys. Increased protein expression of wnt1, β-catenin, snail, desmin, and α-SMA, as well as decreased protein expression of nephrin was detected in diabetic kidneys. All these abnormalities found in DN rats were partially restored by PN treatment.

Conclusion

PN ameliorated albuminuria and podocyte EMT in diabetic rats partly through inhibiting Wnt/β-catenin signaling pathway. These findings provide experimental arguments for a novel therapeutic option in DN.

Keywords:

• Panax notoginseng
• diabetic nephropathy
• podocyte
• Wnt/β-catenin
• epithelial–mesenchymal transition

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (81774052 and 81573738), the Pudong New Area Science and Technology Commission (PKJ2015-Y10). This work was also sponsored by the Shanghai Pujiang Program (17PJD031) and Three-year action plan for Shanghai further accelerating the development of traditional Chinese medicine (ZY (2018-2020)-CCCX-4007).

Disclosure

The authors report no conflicts of interest in this work.