ID | 60131 |
フルテキストURL | |
著者 |
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
|
抄録 | 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.
|
キーワード | semaphorin3A
podocyte
proteinuria
apoptosis
c-Jun N-terminal kinase
|
発行日 | 2020-06-08
|
出版物タイトル |
International Journal of Molecular Sciences
|
巻 | 21巻
|
号 | 11号
|
出版者 | MDPI
|
開始ページ | 4099
|
ISSN | 1422-0067
|
NCID | AA12038549
|
資料タイプ |
学術雑誌論文
|
言語 |
英語
|
OAI-PMH Set |
岡山大学
|
著作権者 | © 2020 by the authors.
|
論文のバージョン | publisher
|
PubMed ID | |
DOI | |
Web of Science KeyUT | |
関連URL | isVersionOf https://doi.org/10.3390/ijms21114099
|
ライセンス | http://creativecommons.org/licenses/by/4.0/
|
助成機関名 |
文部科学省
|
助成番号 | 18K08244
18K15978
|