Abstract

Podocytopathies are kidney diseases that are driven by podocyte injury with proteinuria and proteinuria-related symptoms as the main clinical presentations. Albeit podocytopathies are the major contributors to end-stage kidney disease, the underlying molecular mechanisms of podocyte injury remain to be elucidated. Mitochondrial oxidative stress is associated with kidney diseases, and increasing evidence suggests that oxidative stress plays a vital role in the pathogenesis of podocytopathies. Accumulating evidence has placed mitochondrial oxidative stress in the focus of cell death research. Excessive generated reactive oxygen species over antioxidant defense under pathological conditions lead to oxidative damage to cellular components and regulate cell death in the podocyte. Conversely, exogenous antioxidants can protect podocyte from cell death. This review provides an overview of the role of mitochondrial oxidative stress in podocytopathies and discusses its role in the cell death of the podocyte, aiming to identify the novel targets to improve the treatment of patients with podocytopathies.

Highlights

  • Podocytopathies are defined as kidney diseases that are driven by podocyte injury with proteinuria and proteinuria-related symptoms as the main clinical features [1]

  • Since reactive oxygen species (ROS)-mediated cell death is of great importance for the pathogenesis of podocytopathies, antioxidants that can protect the podocyte from death are promising for the treatment of patients diagnosed with podocytopathies

  • The evidence supports the determination that mitochondrial oxidative stress, driven by excessive stress and harmful stimuli to the podocyte, plays an essential role in the pathogenesis of podocytopathies

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Summary

Introduction

Podocytopathies are defined as kidney diseases that are driven by podocyte injury with proteinuria and proteinuria-related symptoms as the main clinical features [1]. Excessive stress and harmful stimuli are likely to cause podocyte injury, possibly even death, which is clinically characterized by proteinuria and pathologically characterized by podocyte foot process effacement (FPE), detachment, and loss [1,2]. Considering the poor proliferation capacity of the podocyte, excessive podocyte loss progressively aggravates podocyte damage and eventually leads to global glomerulosclerosis [2]. Understanding how such detrimental stress and stimuli cause podocyte injury can help us to advance our acknowledgement of the mechanisms underlying the occurrence and progression of podocytopathies. This review provides an overview of the role of mitochondrial oxidative stress in podocytopathies and discusses its role in the cell death of the podocyte, aiming to identify novel targets to improve the treatment of patients with podocytopathies

Spectrum of Podocytopathies
Oxidative Stress in Podocytopathies
Elevated ROS Production
Deficient Antioxidant Defense Systems
Oxidative Stress and Cell Death in Podocytopathies
Molecular
Therapeutic Implications
Findings
Conclusions
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