Kidney Week

Abstract: PO0706

Wnt5a-Ca2+ Non-Canonical Pathway Mediates Mitochondrial Dysfunction in the Progression of Diabetic Nephropathy via Mitochondrial Calcium Uniporter

Session Information

• Diabetic Kidney Disease: Basic - II
  November 04, 2021 | Location: On-Demand, Virtual Only
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 601 Diabetic Kidney Disease: Basic

Authors

• Fei, Yang, Shanghai Sixth Peoples Hospital, Shanghai, Shanghai, China

Yang Fei,

• Fan, Ying, Shanghai Sixth Peoples Hospital, Shanghai, Shanghai, China

Ying Fan,

• Zhang, Qunzi, Shanghai Sixth Peoples Hospital, Shanghai, Shanghai, China

Qunzi Zhang,

• Wang, Niansong, Shanghai Sixth Peoples Hospital, Shanghai, Shanghai, China

Niansong Wang,

Background

Mitochondrial abnormalities play crucial roles in diabetic tubular injury progression. Abnormal expression of Wnt5a has been detected in many metabolic diseases. However, the association of Wnt5a and mitochondrial dysfunction in diabetic nephropathy (DN) progression remains unknown.

Methods

Diabetic DBA2/J mice induced by streptozotocin were assigned to amlodipine (5mg/kg/d) and losartan (10mg/kg/d) for eight weeks. The expression of Wnt5a, mitochondrial dynamics associated proteins (Drp1 and Mfn2), mitochondrial calcium uniporter (MCU) were examined through Western blot and immunohistochemistry in kidney of STZ-induced diabetic and high glucose stimulated HK-2 cells. Calcium concentration in cells and mitochondria was detected through specific ELISA kit.

Results

In this study, upregulation of Wnt5a , increase of both cellular and mitochondrial Ca²⁺ , mitochondrial fragmentation and altered mitochondrial dynamics-associated protein expression were detected in the tubules of diabetic mice and in high glucose stimulated HK-2 cells. In vitro, Wnt5a overexpression induced the Ca²⁺ influx and aggravated mitochondrial fusion-fission disorder. After amlodipine treatment, this Wnt5a-Ca²⁺ pathway was restored, mitochondrial dynamics and morphological changes was improved. Additionally, increase of MCU was also observed in the mitochondrial of tubular cells in DN, suggesting a possible link between Wnt5a-Ca²⁺ pathway and mitochondrial dysfunction.

Conclusion

Our study presented that Wnt5a-Ca2+ signaling pathway might be involved in mitochondrial dysfunction in the progression of DN, and MCU was possibly recognized as the important link during the regulation.