2. Academic Validation
  3. Statins attenuate cholesterol-induced ROS via inhibiting NOX2/NOX4 and mitochondrial pathway in collecting ducts of the kidney

Statins attenuate cholesterol-induced ROS via inhibiting NOX2/NOX4 and mitochondrial pathway in collecting ducts of the kidney

  • BMC Nephrol. 2022 May 13;23(1):184. doi: 10.1186/s12882-022-02815-6.
Ani Wang 1,  Yu Lin 2,  Baien Liang 3 4,  Xiaoduo Zhao 3 4,  Miaojuan Qiu 5,  Hui Huang 6,  Chunling Li 4,  Weidong Wang 7 8,  Yonglun Kong 9 10
Affiliations

Affiliations

  • 1 Cardiovascular Center, The 5thAffiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, China.
  • 2 Department of Pathology, Zhujiang Hospitial, Southern Medical University, Guangzhou, 510282, China.
  • 3 Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74# Zhongshan 2nd Road, Guangzhou, 510080, China.
  • 4 Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China.
  • 5 Research Center, The 7th Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518107, China.
  • 6 Department of Cardiology, The 8th Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518033, China.
  • 7 Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74# Zhongshan 2nd Road, Guangzhou, 510080, China. wangwd6@mail.sysu.edu.cn.
  • 8 Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China. wangwd6@mail.sysu.edu.cn.
  • 9 Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74# Zhongshan 2nd Road, Guangzhou, 510080, China. winlingkong@163.com.
  • 10 Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China. winlingkong@163.com.
PMID: 35562673 DOI: 10.1186/s12882-022-02815-6
Abstract

Background: Statins therapy has been primarily recommended for the prevention of cardiovascular risk in patients with chronic kidney diseases. Statins has also been proved some benefits in lipid-induced kidney diseases. The current study aims to investigate the protection and underlying mechanisms of statins on renal tubular injuries induced by Cholesterol overloaded.

Methods: We used tubular suspensions of inner medullary collecting duct (IMCD) cells from rat kidneys and mouse collecting duct cell line mpkCCD cells to investigate the effect of statins on Reactive Oxygen Species (ROS) production induced by Cholesterol. Protein and mRNA expression of NADPH Oxidase 2 (NOX2) /NOX4 was examined by Western blot and RT-PCR in vitro studies and in rats with 5/6 nephrectomy and high-fat diet. Mitochondrial morphology and membrane potential was observed by Mito-tracker and JC-1.

Results: Statins treatment was associated with decreased NOX2 and NOX4 protein expression and mRNA levels in 5/6Nx rats with high-fat diet. Statins treatment markedly reduced the ROS production in IMCD suspensions and mpkCCD cells. Also, statins reduced NOX2 and NOX4 protein expression and mRNA levels in Cholesterol overload mpkCCD cells and improved mitochondrial morphology and function.

Conclusion: Statins prevented ROS production induced by Cholesterol in the kidney, likely through inhibiting NOXs protein expression and improving mitochondrial function. Statins may be a therapeutic option in treating obesity-associated kidney diseases.

Keywords

Cholesterol; Collecting ducts; ROS; Statins.

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