2. Academic Validation
  3. Tubular Mas receptor mediates lipid-induced kidney injury

Tubular Mas receptor mediates lipid-induced kidney injury

  • Cell Death Dis. 2021 Jan 21;12(1):110. doi: 10.1038/s41419-020-03375-z.
Yonglun Kong 1,  Xiaoduo Zhao 1,  Miaojuan Qiu 1 2,  Yu Lin 3,  Pinning Feng 4,  Suchun Li 1,  Baien Liang 1,  Qing Zhu 5,  Hui Huang 6,  Chunling Li 7,  Weidong Wang 8 9
Affiliations

Affiliations

  • 1 Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
  • 2 Research Center, The Seventh Affliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China.
  • 3 Department of Pathology, Zhujiang Hospitial, Southern Medical University, Guangzhou, 510282, China.
  • 4 Department of Clinical Laboratory, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  • 5 Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
  • 6 Department of Cardiology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518033, China.
  • 7 Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. lichl3@mail.sysu.edu.cn.
  • 8 Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. wangwd6@mail.sysu.edu.cn.
  • 9 Department of Nephrology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China. wangwd6@mail.sysu.edu.cn.
PMID: 33479200 DOI: 10.1038/s41419-020-03375-z
Abstract

Obesity-related kidney diseases are becoming serious health problems worldwide, yet the mechanism by which obesity causes kidney injury is not fully understood. The purpose of current study was to investigate the role of Mas receptor in lipid-induced kidney injury. In mice fed with high-fat diet (HFD), the protein abundance of markers of Autophagy, endoplasmic reticulum stress (ER stress) and Apoptosis was dramatically increased in the kidney cortex, which was markedly prevented by Mas deletion (Mas-/-) or Mas receptor antagonist A779. Palmitic acid (PA) induced persistently increased Autophagy, ER stress, and Apoptosis as well as mitochondrial injuries in primary cultured proximal tubular cells from wild type, but not from Mas-/- mice. In human proximal tubular HK2 cells, PA-induced Autophagy and ER stress was aggravated by Mas agonists Ang (1-7) or AVE0991, but attenuated by A779 or Mas knockdown. Stimulation of Mas resulted in elevated intracellular calcium levels [CA2+]i in HK2 cells treated with PA, whereas inhibition or knockdown of Mas decreased [CA2+]i. Mitochondrial outer membrane located voltage-dependent anion channel (VDAC1) was markedly upregulated in HK2 cells treated with PA, which was associated with impaired mitochondrial morphology and depolarization. These were enhanced by AVE0991 and suppressed by A779 or Mas knockdown. Mas knockdown in HK2 cells prevented impaired interactions among VDAC1, Autophagy adaptor p62, and ubiquitin, induced by PA, leading to a potential ubiquitination of VDAC1. In conclusion, Mas receptor-mediated lipid-induced impaired Autophagy and ER stress in the kidney, likely contributing to tubular injuries in obesity-related kidney diseases.

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  • HY-15534
    99.0%, 线粒体膜电位探针
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