Sphingosine-1-Phosphate Metabolism and Signaling in Kidney Diseases

J Am Soc Nephrol. 2021 Jan;32(1):9-31. doi: 10.1681/ASN.2020050697. Epub 2020 Dec 18.

Abstract

In the past few decades, sphingolipids and sphingolipid metabolites have gained attention because of their essential role in the pathogenesis and progression of kidney diseases. Studies in models of experimental and clinical nephropathies have described accumulation of sphingolipids and sphingolipid metabolites, and it has become clear that the intracellular sphingolipid composition of renal cells is an important determinant of renal function. Proper function of the glomerular filtration barrier depends heavily on the integrity of lipid rafts, which include sphingolipids as key components. In addition to contributing to the structural integrity of membranes, sphingolipid metabolites, such as sphingosine-1-phosphate (S1P), play important roles as second messengers regulating biologic processes, such as cell growth, differentiation, migration, and apoptosis. This review will focus on the role of S1P in renal cells and how aberrant extracellular and intracellular S1P signaling contributes to the pathogenesis and progression of kidney diseases.

Keywords: ceramide; kidney disease; sphingolipid metabolism; sphingolipids; sphingosine-1-phosphate.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis
  • Cell Cycle
  • Cell Differentiation
  • Cell Movement
  • Gene Expression Regulation*
  • Glomerular Filtration Rate
  • Humans
  • Kidney / metabolism*
  • Kidney Diseases / metabolism*
  • Kidney Transplantation
  • Lysophospholipids / metabolism*
  • Membrane Microdomains / metabolism
  • Mice
  • Second Messenger Systems
  • Signal Transduction*
  • Sphingolipids / metabolism
  • Sphingosine / analogs & derivatives*
  • Sphingosine / metabolism

Substances

  • Lysophospholipids
  • Sphingolipids
  • sphingosine 1-phosphate
  • Sphingosine