Article

Podoplanin mediates the renoprotective effect of berberine on diabetic kidney disease in mice

Authors: Jing Yu1, Guan-nan Zong2, Hao Wu3, Ke-qin Zhang2
1 Department of Physiology and Pathophysiology, Tianjin Medical University, 300070 Tianjin, China
2 Department of Endocrinology and Metabolism, Tongji Hospital, Tongji University School of Medicine, 200065 Shanghai, China
3 Department of Cardiology, Tianjin Union Medical Center, Nankai University Affiliated Hospital, 300222 Tianjin, China
Correspondence to: Ke-qin Zhang: keqzhang2018@163.com,
DOI: 10.1038/s41401-019-0263-3
Received: 17 November 2018
Accepted: 22 May 2019
Advance online: 3 July 2019

Abstract

Hyperglycemia-caused podocyte injury plays a crucial role in the progress of diabetic kidney disease. Podoplanin, one of the podocyte-associated molecules, is closely related to the integrity of the glomerular filtration barrier. A number of studies demonstrate that berberine could ameliorate renal dysfunction in diabetic mice with nephropathy, but the molecular mechanisms have not been fully elucidated. In this study, we explored the relationship between the renoprotective effect of berberine and podoplanin expression in streptozotocin (STZ)-induced diabetic mice as well as mouse podocytes (MPC5 cells) cultured in high glucose (HG, 30 mM) medium. We found that the expression levels of podoplanin were significantly decreased both in the renal glomerulus of STZ-induced diabetic mice and HG-cultured MPC5 cells. We also demonstrated that NF-κB signaling pathway was activated in MPC5 cells under HG condition, which downregulated the expression level of podoplanin, thus leading to increased podocyte apoptosis. Administration of berberine (100, 200 mg/kg every day, ig, for 8 weeks) significantly improved hyperglycemia and the renal function of STZ-induced diabetic mice and restored the expression level of podoplanin in renal glomerulus. In high glucose-cultured MPC5 cells, treatment with berberine (30–120 μM) dose-dependently decreased the apoptosis rate, increased the expression of podoplanin, and inhibited the activation of NF-κB signaling pathway. When podoplanin expression was silenced with shRNA, berberine treatment still inhibited the NF-κB signaling pathway, but its antiapoptotic effect on podocytes almost disappeared. Our results suggest that berberine inhibits the activation of NF-κB signaling pathway, thus increasing the podoplanin expression to exert renoprotective effects.
Keywords: podoplanin; berberine; diabetic kidney disease; renoprotective effects; podocytes; apoptosis

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