Sulfatase 2 Is Associated with Steroid Resistance in Childhood Nephrotic Syndrome.
FSGS
glucocorticoids
steroid resistant nephrotic syndrome
sulfatase 2
vascular endothelial growth factor (VEGF)
Journal
Journal of clinical medicine
ISSN: 2077-0383
Titre abrégé: J Clin Med
Pays: Switzerland
ID NLM: 101606588
Informations de publication
Date de publication:
02 Feb 2021
02 Feb 2021
Historique:
received:
30
12
2020
revised:
20
01
2021
accepted:
23
01
2021
entrez:
5
2
2021
pubmed:
6
2
2021
medline:
6
2
2021
Statut:
epublish
Résumé
Glucocorticoid (GC) resistance complicates the treatment of ~10-20% of children with nephrotic syndrome (NS), yet the molecular basis for resistance remains unclear. We used RNAseq analysis and in silico algorithm-based approaches on peripheral blood leukocytes from 12 children both at initial NS presentation and after ~7 weeks of GC therapy to identify a 12-gene panel able to differentiate steroid resistant NS (SRNS) from steroid-sensitive NS (SSNS). Among this panel, subsequent validation and analyses of one biologically relevant candidate, sulfatase 2 (SULF2), in up to a total of 66 children, revealed that both SULF2 leukocyte expression and plasma arylsulfatase activity Post/Pre therapy ratios were greater in SSNS vs. SRNS. However, neither plasma SULF2 endosulfatase activity (measured by VEGF binding activity) nor plasma VEGF levels, distinguished SSNS from SRNS, despite VEGF's reported role as a downstream mediator of SULF2's effects in glomeruli. Experimental studies of NS-related injury in both rat glomeruli and cultured podocytes also revealed decreased SULF2 expression, which were partially reversible by GC treatment of podocytes. These findings together suggest that SULF2 levels and activity are associated with GC resistance in NS, and that SULF2 may play a protective role in NS via the modulation of downstream mediators distinct from VEGF.
Identifiants
pubmed: 33540508
pii: jcm10030523
doi: 10.3390/jcm10030523
pmc: PMC7867139
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK075533
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM127701
Pays : United States
Organisme : National Science Foundation
ID : DBI 1661391
Organisme : NIGMS NIH HHS
ID : U01 GM092655
Pays : United States
Organisme : American Heart Association
ID : CDA34110287
Organisme : NIDDK NIH HHS
ID : R01DK095059-05
Pays : United States
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