1. Academic Validation
  2. Nestin protects podocyte from injury in lupus nephritis by mitophagy and oxidative stress

Nestin protects podocyte from injury in lupus nephritis by mitophagy and oxidative stress

  • Cell Death Dis. 2020 May 5;11(5):319. doi: 10.1038/s41419-020-2547-4.
Yuexin Tian 1 Huifang Guo 2 Xinyan Miao 1 Jie Xu 1 Ran Yang 3 Lu Zhao 1 Jinxi Liu 1 Lin Yang 4 Fan Gao 1 Wei Zhang 1 Qingjuan Liu 1 Shaoguang Sun 5 Yu Tian 1 Hongbo Li 1 Jie Huang 1 Cunyang Gu 1 Shuxia Liu 6 Xiaojuan Feng 7
Affiliations

Affiliations

  • 1 Department of Pathology, Hebei Key Laboratory of Nephrology, Center of Metabolic Diseases and Cancer Research, Hebei Medical University, 050017, Shijiazhuang, China.
  • 2 Department of Rheumatology, The Second Hospital of Hebei Medical University, 050017, Shijiazhuang, China.
  • 3 Department of Pathology, Hebei Province Hospital of Chinese Medicine, 050017, Shijiazhuang, China.
  • 4 Department of Nephrology, The Second Hospital of Hebei Medical University, 050017, Shijiazhuang, China.
  • 5 Department of Biochemistry and Molecular Biology, Hebei Medical University, 050017, Shijiazhuang, China.
  • 6 Department of Pathology, Hebei Key Laboratory of Nephrology, Center of Metabolic Diseases and Cancer Research, Hebei Medical University, 050017, Shijiazhuang, China. shuxialiu@hebmu.edu.cn.
  • 7 Department of Pathology, Hebei Key Laboratory of Nephrology, Center of Metabolic Diseases and Cancer Research, Hebei Medical University, 050017, Shijiazhuang, China. fengxiaojuan1985@163.com.
Abstract

Podocyte injury is the main cause of proteinuria in lupus nephritis (LN). Nestin, an important Cytoskeleton protein, is expressed stably in podocytes and is associated with podocyte injury. However, the role of nestin in the pathogenesis of proteinuria in LN remains unclear. The correlations among nestin, nephrin and proteinuria were analyzed in LN patients and MRL/lpr lupus-prone mice. The expression of nestin in mouse podocyte lines (MPCs) and MRL/lpr mice was knocked down to determine the role of nestin in podocyte injury. Inhibitors and RNAi method were used to explore the role of Mitophagy and oxidative stress in nestin protection of podocyte from damage. There was a significantly negative correlation between nestin and proteinuria both in LN patients and MRL/lpr mice, whereas the expression of nephrin was positively correlated with nestin. Knockdown of nestin resulted in not only the decrease of nephrin, p-nephrin (Y1217) and mitophagy-associated proteins in cultured podocytes and the podocytes of MRL/lpr mice, but also mitochondrial dysfunction in podocytes stimulated with LN plasma. The expression and phosphorylation of nephrin was significantly decreased by reducing the level of Mitophagy or production of Reactive Oxygen Species (ROS) in cultured podocytes. Our findings suggested that nestin regulated the expression of nephrin through Mitophagy and oxidative stress to protect the podocytes from injury in LN.

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