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Sang, Yizhen Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Tsuji, Kenji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences ORCID Kaken ID researchmap
Inoue-Torii, Akiko Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Fukushima, Kazuhiko Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kitamura, Shinji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kaken ID publons
Wada, Jun Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate ORCID Kaken ID publons researchmap
Abstract
Podocyte injury is an independent risk factor for the progression of renal diseases. Semaphorin3A (SEMA3A), expressed in podocytes and tubular cells in the mammalian adult kidneys, has been reported to regulate diverse biological functions and be associated with renal diseases. Here, we investigated pathological roles of SEMA3A signaling on podocyte injury using a doxorubicin (Dox)-induced mouse model and examined the therapeutic effect of SEMA3A-inhibitor (SEMA3A-I). We demonstrated that Dox caused massive albuminuria and podocyte apoptosis as well as an increase of SEMA3A expression in podocytes, all of which were ameliorated with SEMA3A-I treatment. In addition, c-Jun N-terminal kinase (JNK), known as a downstream of SEMA3A signaling, was activated in Dox-injected mouse podocytes while SEMA3A-I treatment partially blocked the activation. In vitro, SEMA3A-I protected against Dox-induced podocyte apoptosis and recombinant SEMA3A caused podocyte apoptosis with activation of JNK signaling. JNK inhibitor, SP600125, attenuated SEMA3A-induced podocyte apoptosis, indicating that the JNK pathway would be involved in SEMA3A-induced podocyte apoptosis. Furthermore, the analysis of human data revealed a positive correlation between levels of urinary SEMA3A and protein, suggesting that SEMA3A is associated with podocyte injury. In conclusion, SEMA3A has essential roles in podocyte injury and it would be the therapeutic target for protecting from podocyte injury.
Keywords
semaphorin3A
podocyte
proteinuria
apoptosis
c-Jun N-terminal kinase
Published Date
2020-06-08
Publication Title
International Journal of Molecular Sciences
Volume
volume21
Issue
issue11
Publisher
MDPI
Start Page
4099
ISSN
1422-0067
NCID
AA12038549
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
Copyright Holders
© 2020 by the authors.
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publisher
PubMed ID
DOI
Web of Science KeyUT
Related Url
isVersionOf https://doi.org/10.3390/ijms21114099
License
http://creativecommons.org/licenses/by/4.0/
Funder Name
Ministry of Education, Culture, Sports, Science and Technology
助成番号
18K08244
18K15978