Sphingosine-1-Phosphate Metabolism and Signaling in Kidney Diseases

Drexler, Yelena; Molina, Judith; Mitrofanova, Alla; Fornoni, Alessia; Merscher, Sandra

doi:10.1681/asn.2020050697

Cited by 34 publications

(29 citation statements)

References 261 publications

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“…Among the different bioactive sphingolipid, C1P is less documented in the different physiological systems. On the other hand, sphingosine-1-phosphate, which may be the most important bioactive lipid, is very well studied in kidney physiology and pathophysiology [2,6,7,67]. As S1P and C1P members are a type of family of signaling molecules with common precursors and sharing mutual interconversion steps, it is possible to imagine that C1P would also be present along the entire nephron.…”

Section: Discussionmentioning

confidence: 99%

Ceramide-1-Phosphate as a Potential Regulator of the Second Sodium Pump from Kidney Proximal Tubules by Triggering Distinct Protein Kinase Pathways in a Hierarchic Way

Cabral

Almeida

Grelle

et al. 2022

CIMB

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Kidney proximal tubules are a key segment in the reabsorption of solutes and water from the glomerular ultrafiltrate, an essential process for maintaining homeostasis in body fluid compartments. The abundant content of Na+ in the extracellular fluid determines its importance in the regulation of extracellular fluid volume, which is particularly important for different physiological processes including blood pressure control. Basolateral membranes of proximal tubule cells have the classic Na+ + K+-ATPase and the ouabain-insensitive, K+-insensitive, and furosemide-sensitive Na+-ATPase, which participate in the active Na+ reabsorption. Here, we show that nanomolar concentrations of ceramide-1 phosphate (C1P), a bioactive sphingolipid derived in biological membranes from different metabolic pathways, promotes a strong inhibitory effect on the Na+-ATPase activity (C1P50 ≈ 10 nM), leading to a 72% inhibition of the second sodium pump in the basolateral membranes. Ceramide-1-phosphate directly modulates protein kinase A and protein kinase C, which are known to be involved in the modulation of ion transporters including the renal Na+-ATPase. Conversely, we did not observe any effect on the Na+ + K+-ATPase even at a broad C1P concentration range. The significant effect of ceramide-1-phosphate revealed a new potent physiological and pathophysiological modulator for the Na+-ATPase, participating in the regulatory network involving glycero- and sphingolipids present in the basolateral membranes of kidney tubule cells.

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Section: Discussionmentioning

confidence: 99%

Ceramide-1-Phosphate as a Potential Regulator of the Second Sodium Pump from Kidney Proximal Tubules by Triggering Distinct Protein Kinase Pathways in a Hierarchic Way

Cabral

Almeida

Grelle

et al. 2022

CIMB

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“…Notably, accumulating data suggest that the cellular response to S1P differs depending on whether S1P is bound to apoM or albumin ( 65 ). S1P bound to apoM promote a more sustained effect on barrier function compared to S1P bound to albumin, due to a reduction in S1P1 degradation ( 66 ).…”

Section: S1p Expression Secretion and Signalingmentioning

confidence: 99%

“…While the association between S1P and kidney function has been poorly studied, the mechanistic role of S1P signaling in kidney disease has been extensively addressed in animal models, recently reviewed in detail by Drexler et al ( 65 ). Thus, in the present review, only a brief summary of the overall trends is provided.…”

Section: The Apom/s1p Axis—a Mediator Of Kidney Disease?mentioning

confidence: 99%

The apoM/S1P Complex—A Mediator in Kidney Biology and Disease?

Bisgaard

Christoffersen

2021

Front. Med.

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Kidney disease affects more than 10% of the population, can be both acute and chronic, and is linked to other diseases such as cardiovascular disease, diabetes, and sepsis. Despite the detrimental consequences for patients, no good treatment options directly targeting the kidney are available. Thus, a better understanding of the pathology and new treatment modalities are required. Accumulating evidence suggests that the apolipoprotein M/sphingosine−1-phosphate (apoM/S1P) axis is a likely drug target, but significant gaps in our knowledge remain. In this review, we present what has so far been elucidated about the role of apoM in normal kidney biology and describe how changes in the apoM/S1P axis are thought to affect the development of kidney disease. ApoM is primarily produced in the liver and kidneys. From the liver, apoM is secreted into circulation, where it is attached to lipoproteins (primarily HDL). Importantly, apoM is a carrier of the bioactive lipid S1P. S1P acts by binding to five different receptors. Together, apoM/S1P plays a role in several biological mechanisms, such as inflammation, endothelial cell permeability, and lipid turnover. In the kidney, apoM is primarily expressed in the proximal tubular cells. S1P can be produced locally in the kidney, and several of the five S1P receptors are present in the kidney. The functional role of kidney-derived apoM as well as plasma-derived apoM is far from elucidated and will be discussed based on both experimental and clinical studies. In summary, the current studies provide evidence that support a role for the apoM/S1P axis in kidney disease; however, additional pre-clinical and clinical studies are needed to reveal the mechanisms and target potential in the treatment of patients.

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“…The role of sphingolipids in the pathogenesis of kidney diseases has been comprehensively reviewed [ 11 , 27 ]. Sphingolipid accumulation in glomerular disease of genetic origin was elaborated in detail elsewhere [ 27 ].…”

Section: Hereditary Diseases Support a Role Of Lipid Dysmetabolism In The Development Of Nephrotic Syndrome (Ns)mentioning

confidence: 99%

“…We will provide an insight into the potential use of these agents as therapeutic therapies. Of the many lipid-relevant pathways of interest, we will focus our attention on cholesterol and fatty acid metabolism as we recently reviewed the role of sphingolipids in the progression of kidney diseases elsewhere [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Use of Lipid-Modifying Agents for the Treatment of Glomerular Diseases

Merscher

Fornoni

2021

JPM

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Although dyslipidemia is associated with chronic kidney disease (CKD), it is more common in nephrotic syndrome (NS), and guidelines for the management of hyperlipidemia in NS are largely opinion-based. In addition to the role of circulating lipids, an increasing number of studies suggest that intrarenal lipids contribute to the progression of glomerular diseases, indicating that proteinuric kidney diseases may be a form of “fatty kidney disease” and that reducing intracellular lipids could represent a new therapeutic approach to slow the progression of CKD. In this review, we summarize recent progress made in the utilization of lipid-modifying agents to lower renal parenchymal lipid accumulation and to prevent or reduce kidney injury. The agents mentioned in this review are categorized according to their specific targets, but they may also regulate other lipid-relevant pathways.

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Sphingosine-1-Phosphate Metabolism and Signaling in Kidney Diseases

Cited by 34 publications

References 261 publications

Ceramide-1-Phosphate as a Potential Regulator of the Second Sodium Pump from Kidney Proximal Tubules by Triggering Distinct Protein Kinase Pathways in a Hierarchic Way

Ceramide-1-Phosphate as a Potential Regulator of the Second Sodium Pump from Kidney Proximal Tubules by Triggering Distinct Protein Kinase Pathways in a Hierarchic Way

The apoM/S1P Complex—A Mediator in Kidney Biology and Disease?

Use of Lipid-Modifying Agents for the Treatment of Glomerular Diseases

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