Translational Aspects of Sphingolipid Metabolism in Renal Disorders

Abstract

Sphingolipids, long thought to be passive components of biological membranes with merely a structural role, have proved throughout the past decade to be major players in the pathogenesis of many human diseases. The study and characterization of several genetic disorders like Fabry’s and Tay Sachs, where sphingolipid metabolism is disrupted, leading to a systemic array of clinical symptoms, have indeed helped elucidate and appreciate the importance of sphingolipids and their metabolites as active signaling molecules. In addition to being involved in dynamic cellular processes like apoptosis, senescence and differentiation, sphingolipids are implicated in critical physiological functions such as immune responses and pathophysiological conditions like inflammation and insulin resistance. Interestingly, the kidneys are among the most sensitive organ systems to sphingolipid alterations, rendering these molecules and the enzymes involved in their metabolism, promising therapeutic targets for numerous nephropathic complications that stand behind podocyte injury and renal failure.

Modulation of DNA Damage Response by Sphingolipid Signaling: An Interplay that Shapes Cell Fate

“…Sphingolipids are no longer thought to be only major structural components of biological membranes but have recently proven to be, along with their active metabolites (sphingomyelin, ceramide, sphingosine, sphingosine-1-phosphate, ceramide-1-phosphate), key players in various human diseases [ 99 , 100 ]. These bioactive signaling molecules mediate various important biological processes such as cell growth, survival, senescence, inflammatory responses, and death by regulating their downstream targets [ 4 , 101 ].…”

APOL1 polymorphism modulates sphingolipid profile of human podocytes

“…These enzymes are diversely expressed in different types of human cells in order to achieve the cell specific SL plasma membrane functions. Indeed, alterations in the SLs pattern are usually associated with pathological conditions including podocyte injury [32].…”

Modulation of radiation‐induced damage of human glomerular endothelial cells by SMPDL3B

“…There has been extensive research in the past decade conducted by our laboratory and others in an attempt to decipher the molecular mechanisms involved in the development of nephropathies 6‐9 . Prior work identified the glomerulus to be a key player in renal failure 10 .…”

“…Prior work identified the glomerulus to be a key player in renal failure 10 . Among the different glomerular cells, podocytes have received considerable attention during the development of various nephrotic and nephritic syndromes 7 . However, other components of the glomerular filtration barrier (GFB), namely the human glomerular endothelial cells (GEnC), remain poorly investigated, despite being constantly recognized as key players in primary and secondary glomerular diseases.…”