Tanshinone IIA is superior to paricalcitol in ameliorating tubulointerstitial fibrosis through regulation of VDR/Wnt/β-catenin pathway in rats with diabetic nephropathy

Jing-Yi Zeng; Yu Wang; Fu-Yuan Hong; Miao Miao; Yu-Ying Jiang; Zi-Xuan Qiao; Yun-Tao Wang; Xiao-Rong Bao

doi:10.1007/s00210-023-02853-3

Tanshinone IIA is superior to paricalcitol in ameliorating tubulointerstitial fibrosis through regulation of VDR/Wnt/β-catenin pathway in rats with diabetic nephropathy

Naunyn Schmiedebergs Arch Pharmacol. 2023 Nov 22. doi: 10.1007/s00210-023-02853-3. Online ahead of print.

Authors

Jing-Yi Zeng^{1

2}, Yu Wang², Fu-Yuan Hong¹, Miao Miao², Yu-Ying Jiang², Zi-Xuan Qiao², Yun-Tao Wang², Xiao-Rong Bao³

Affiliations

¹ Department of Nephrology, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
² Department of Nephrology, Jinshan Hospital of Fudan University, Shanghai, China.
³ Department of Nephrology, Jinshan Hospital of Fudan University, Shanghai, China. xrbao19660108@163.com.

PMID: 37991543
DOI: 10.1007/s00210-023-02853-3

Abstract

Glomerulosclerosis and tubulointerstitial fibrosis (TIF) are closely involved in the development of diabetic nephropathy (DN). Moreover, the development of TIF is closely related to epithelial-to-mesenchymal transition (EMT). Tanshinone IIA (Tan) has various pharmacological effects, especially the anti-fibrotic effect. And it is mainly used in the clinical treatment of cardiovascular diseases. Currently, the protective effect of Tan on DN and its possible mechanism have not been clearly elucidated. Our previous studies illustrated that Tan could improve the EMT of HK-2 cells induced by high glucose by regulating the vitamin D receptor (VDR)/Wnt/β-catenin pathway. Here, we collected demographic information and laboratory results from the National Health and Nutrition Examination Survey (NHANES) database in order to investigate the relationship between VD and DN. Then, we established a DN model and treated DN rats with Tan and paricalcitol (Par) for 6 weeks. We subsequently compared the changes in general condition, renal function, pathological changes, and TIF-related protein expression levels of control rats, DN rats induced by STZ, DN rats with Tan at 5.4 mg/kg, DN rats with Tan at 10.8 mg/kg, and DN rats with Par at 0.054 µg/kg, to explore the effect and mechanism of Tan and Par on DN rats. The results showed that VD had a protective effect against DN in diabetic patients. And we found that Tan had a protective effect on renal fibrosis in DN rats, which was superior to Par in improving the symptoms of "three more and one less," reducing fasting blood glucose level, improving renal index, BUN/SCr, and UACR, reducing histopathological damage of kidney, and improving the expression of fibrosis-related proteins in kidney tissue by regulating VDR/Wnt/β-catenin pathway. Tan was superior to Par in ameliorating tubulointerstitial fibrosis by regulating VDR/Wnt/β-catenin pathway in rats with diabetic nephropathy.

Keywords: Diabetic nephropathy; Paricalcitol; Tanshinone IIA; Tubulointerstitial fibrosis; VDR/Wnt/β-catenin pathway.

Abstract

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