Consistent alteration of chain length-specific ceramides in human and mouse fibrotic kidneys.
Actins
/ genetics
Adenine
/ administration & dosage
Aged
Animals
Biomarkers
/ metabolism
Ceramides
/ classification
Collagen Type I
/ genetics
Collagen Type I, alpha 1 Chain
Collagen Type III
/ genetics
Disease Models, Animal
Female
Fibrosis
Gene Expression Regulation
Humans
Hydronephrosis
/ chemically induced
Kidney
/ metabolism
Lipid Metabolism
/ genetics
Male
Mice
Mice, Inbred C57BL
Middle Aged
Pyelonephritis
/ chemically induced
Sphingolipids
/ classification
Ureteral Obstruction
/ genetics
Ceramide
Fibrosis
Kidney
Lipid mediator
Nephropathy
Sphingolipids
Journal
Biochimica et biophysica acta. Molecular and cell biology of lipids
ISSN: 1879-2618
Titre abrégé: Biochim Biophys Acta Mol Cell Biol Lipids
Pays: Netherlands
ID NLM: 101731727
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
09
06
2020
revised:
16
09
2020
accepted:
23
09
2020
pubmed:
4
10
2020
medline:
14
4
2021
entrez:
3
10
2020
Statut:
ppublish
Résumé
Several studies revealed alterations of single sphingolipid species, such as chain length-specific ceramides, in plasma and serum of patients with kidney diseases. Here, we investigated whether such alterations occur in kidney tissue from patients and mice suffering from renal fibrosis, the common endpoint of chronic kidney diseases. Human fibrotic kidney samples were collected from nephrectomy specimens with hydronephrosis and/or pyelonephritis. Healthy parts from tumor nephrectomies served as nonfibrotic controls. Mouse fibrotic kidney samples were collected from male C57BL/6J mice treated with an adenine-rich diet for 14 days or were subjected to 7 days of unilateral ureteral obstruction (UUO). Kidneys of untreated mice and contralateral kidneys (UUO) served as respective controls. Sphingolipid levels were detected by LC-MS/MS. Fibrotic markers were analyzed by TaqMan® analysis and immunohistology. Very long-chain ceramides Cer d18:1/24:0 and Cer d18:1/24:1 were significantly downregulated in both fibrotic human kidney cortex and fibrotic murine kidney compared to respective control samples. These effects correlate with upregulation of COL1α1, COL3α1 and αSMA expression in fibrotic human kidney cortex and fibrotic mouse kidney. We have shown that very long-chain ceramides Cer d18:1/24:0 and Cer d18:1/24:1 are consistently downregulated in fibrotic kidney samples from human and mouse. Our findings support the use of in vivo murine models as appropriate translational means to understand the involvement of ceramides in human kidney diseases. In addition, our study raises interesting questions about the possible manipulation of ceramide metabolism to prevent progression of fibrosis and the use of ceramides as potential biomarkers of chronic kidney disease.
Sections du résumé
BACKGROUND
Several studies revealed alterations of single sphingolipid species, such as chain length-specific ceramides, in plasma and serum of patients with kidney diseases. Here, we investigated whether such alterations occur in kidney tissue from patients and mice suffering from renal fibrosis, the common endpoint of chronic kidney diseases.
METHODS
Human fibrotic kidney samples were collected from nephrectomy specimens with hydronephrosis and/or pyelonephritis. Healthy parts from tumor nephrectomies served as nonfibrotic controls. Mouse fibrotic kidney samples were collected from male C57BL/6J mice treated with an adenine-rich diet for 14 days or were subjected to 7 days of unilateral ureteral obstruction (UUO). Kidneys of untreated mice and contralateral kidneys (UUO) served as respective controls. Sphingolipid levels were detected by LC-MS/MS. Fibrotic markers were analyzed by TaqMan® analysis and immunohistology.
RESULTS
Very long-chain ceramides Cer d18:1/24:0 and Cer d18:1/24:1 were significantly downregulated in both fibrotic human kidney cortex and fibrotic murine kidney compared to respective control samples. These effects correlate with upregulation of COL1α1, COL3α1 and αSMA expression in fibrotic human kidney cortex and fibrotic mouse kidney.
CONCLUSION
We have shown that very long-chain ceramides Cer d18:1/24:0 and Cer d18:1/24:1 are consistently downregulated in fibrotic kidney samples from human and mouse. Our findings support the use of in vivo murine models as appropriate translational means to understand the involvement of ceramides in human kidney diseases. In addition, our study raises interesting questions about the possible manipulation of ceramide metabolism to prevent progression of fibrosis and the use of ceramides as potential biomarkers of chronic kidney disease.
Identifiants
pubmed: 33010454
pii: S1388-1981(20)30213-4
doi: 10.1016/j.bbalip.2020.158821
pii:
doi:
Substances chimiques
ACTA2 protein, human
0
Actins
0
Biomarkers
0
COL3A1 protein, human
0
Ceramides
0
Collagen Type I
0
Collagen Type I, alpha 1 Chain
0
Collagen Type III
0
Sphingolipids
0
Adenine
JAC85A2161
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
158821Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.