Loss of sphingosine kinase 2 enhances Wilm's tumor suppressor gene 1 and nephrin expression in podocytes and protects from streptozotocin-induced podocytopathy and albuminuria in mice.

Albuminuria / genetics Animals Diabetic Nephropathies / genetics Genes, Tumor Suppressor Membrane Proteins Mice Mice, Knockout Phosphotransferases (Alcohol Group Acceptor) Podocytes Streptozocin WT1 Proteins
Diabetic nephropathy Glomerular disease Nephrin Podocytes S1P Sphk2 Wilm's tumor suppressor 1

Journal

Matrix biology : journal of the International Society for Matrix Biology
ISSN: 1569-1802
Titre abrégé: Matrix Biol
Pays: Netherlands
ID NLM: 9432592

Informations de publication

Date de publication:
04 2021
Historique:
received: 26 01 2021
revised: 10 05 2021
accepted: 10 05 2021
pubmed: 21 5 2021
medline: 14 1 2022
entrez: 20 5 2021
Statut: ppublish

Résumé

The sphingosine 1-phosphate (S1P) is a bioactive sphingolipid that is now appreciated as key regulatory factor for various cellular functions in the kidney, including matrix remodeling. It is generated by two sphingosine kinases (Sphk), Sphk1 and Sphk2, which are ubiquitously expressed, but have distinct enzymatic activities and subcellular localizations. In this study, we have investigated the role of Sphk2 in podocyte function and its contribution to diabetic nephropathy. We show that streptozotocin (STZ)-induced nephropathy and albuminuria in mice is prevented by genetic depletion of Sphk2. This protection correlated with an increased protein expression of the transcription factor Wilm's tumor suppressor gene 1 (WT1) and its target gene nephrin, and a reduced macrophage infiltration in immunohistochemical renal sections of STZ-treated Sphk2

Identifiants

DOI: 10.1016/j.matbio.2021.05.003 PMID: 34015468
pubmed: 34015468
pii: S0945-053X(21)00043-3
doi: 10.1016/j.matbio.2021.05.003
pii:
doi:

Substances chimiques

Membrane Proteins 0
WT1 Proteins 0
WT1 protein, mouse 0
nephrin 0
Streptozocin 5W494URQ81
Phosphotransferases (Alcohol Group Acceptor) EC 2.7.1.-
sphingosine kinase EC 2.7.1.-
sphingosine kinase 2, mouse EC 2.7.1.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

32-48

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest None.

Auteurs

Faik Imeri (F)

Institute of Pharmacology, University of Bern, Inselspital, INO-F, Bern CH-3010, Switzerland.

Bisera Stepanovska Tanturovska (B)

Institute of Pharmacology, University of Bern, Inselspital, INO-F, Bern CH-3010, Switzerland.

Stephanie Schwalm (S)

Institute of Pharmacology and Toxicology, Goethe University, Frankfurt am Main D-60590, Germany.

Sarbari Saha (S)

Institute of Pharmacology and Toxicology, Goethe University, Frankfurt am Main D-60590, Germany.

Jinyang Zeng-Brouwers (J)

Institute of Pharmacology and Toxicology, Goethe University, Frankfurt am Main D-60590, Germany.

Herrmann Pavenstädt (H)

Medizinische Klinik D, University Hospital Münster, Münster D-48149, Germany.

Josef Pfeilschifter (J)

Institute of Pharmacology and Toxicology, Goethe University, Frankfurt am Main D-60590, Germany.

Liliana Schaefer (L)

Institute of Pharmacology and Toxicology, Goethe University, Frankfurt am Main D-60590, Germany. Electronic address: schaefer@med.uni-frankfurt.de.

Andrea Huwiler (A)

Institute of Pharmacology, University of Bern, Inselspital, INO-F, Bern CH-3010, Switzerland. Electronic address: Huwiler@pki.unibe.ch.

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Classifications MeSH

questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Manifestations urologiques › Protéinurie › Albuminurie › Loss of sphingosine kinase 2 enhances Wilm's...
questionsmedicales.fr › Eucaryotes › Animaux › Loss of sphingosine kinase 2 enhances Wilm's...
questionsmedicales.fr › Maladies endocriniennes › Diabète › Complications du diabète › Néphropathies diabétiques › Loss of sphingosine kinase 2 enhances Wilm's...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Gènes suppresseurs de tumeur › Loss of sphingosine kinase 2 enhances Wilm's...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Loss of sphingosine kinase 2 enhances Wilm's...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Loss of sphingosine kinase 2 enhances Wilm's...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › Loss of sphingosine kinase 2 enhances Wilm's...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Phosphotransferases › Phosphotransferases (Alcohol Group Acceptor) › Loss of sphingosine kinase 2 enhances Wilm's...
questionsmedicales.fr › Cellules › Cellules épithéliales › Podocytes › Loss of sphingosine kinase 2 enhances Wilm's...
questionsmedicales.fr › Glucides › Hétérosides › Aminosides › Streptozocine › Loss of sphingosine kinase 2 enhances Wilm's...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines suppresseurs de tumeurs › Protéines WT1 › Loss of sphingosine kinase 2 enhances Wilm's...