Sphingolipids and Redox Signaling in Renal Regulation and Chronic Kidney Diseases.

Significance: Sphingolipids play critical roles in the membrane biology and intracellular signaling events that influence cellular behavior and function. Our review focuses on the cellular mechanisms and functional relevance of the cross talk between sphingolipids and redox signaling, which may be critically implicated in the pathogenesis of different renal diseases. Recent Advances: Reactive oxygen species (ROS) and sphingolipids can regulate cellular redox homeostasis through the regulation of NADPH oxidase, mitochondrial integrity, nitric oxide synthase (NOS), and antioxidant enzymes. Over the last two decades, there have been significant advancements in the field of sphingolipid research, and it was in 2010 for the first time that sphingolipid receptor modulator was exploited as a therapeutic in humans. The cross talk of sphingolipids with redox signaling pathways becomes an important mechanism in the development of many different diseases such as renal diseases. Critical Issues: The critical issues to be addressed in this review are how sphingolipids interact with the redox signaling pathway to regulate renal function and even result in chronic kidney diseases. Ceramide, sphingosine, and sphingosine-1-phosphate (S1P) as main signaling sphingolipids are discussed in more detail. Future Directions: Although sphingolipids and ROS may mediate or modulate cellular responses to physiological and pathological stimuli, more translational studies and mechanistic pursuit in a tissue- or cell-specific way are needed to enhance our understanding of this important topic and to develop effective therapeutic strategies to treat diseases associated with redox signaling and sphingolipid cross talk. Antioxid. Redox Signal. 28, 1008-1026.