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Semaphorin3A-Inhibitor Ameliorates Doxorubicin-Induced Podocyte Injury
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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312798/ https://www.ncbi.nlm.nih.gov/pubmed/32521824 http://dx.doi.org/10.3390/ijms21114099 |
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author | Sang, Yizhen Tsuji, Kenji Inoue-Torii, Akiko Fukushima, Kazuhiko Kitamura, Shinji Wada, Jun |
author_facet | Sang, Yizhen Tsuji, Kenji Inoue-Torii, Akiko Fukushima, Kazuhiko Kitamura, Shinji Wada, Jun |
author_sort | Sang, Yizhen |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7312798 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-73127982020-06-26 Semaphorin3A-Inhibitor Ameliorates Doxorubicin-Induced Podocyte Injury Sang, Yizhen Tsuji, Kenji Inoue-Torii, Akiko Fukushima, Kazuhiko Kitamura, Shinji Wada, Jun Int J Mol Sci Article 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. MDPI 2020-06-08 /pmc/articles/PMC7312798/ /pubmed/32521824 http://dx.doi.org/10.3390/ijms21114099 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sang, Yizhen Tsuji, Kenji Inoue-Torii, Akiko Fukushima, Kazuhiko Kitamura, Shinji Wada, Jun Semaphorin3A-Inhibitor Ameliorates Doxorubicin-Induced Podocyte Injury |
title | Semaphorin3A-Inhibitor Ameliorates Doxorubicin-Induced Podocyte Injury |
title_full | Semaphorin3A-Inhibitor Ameliorates Doxorubicin-Induced Podocyte Injury |
title_fullStr | Semaphorin3A-Inhibitor Ameliorates Doxorubicin-Induced Podocyte Injury |
title_full_unstemmed | Semaphorin3A-Inhibitor Ameliorates Doxorubicin-Induced Podocyte Injury |
title_short | Semaphorin3A-Inhibitor Ameliorates Doxorubicin-Induced Podocyte Injury |
title_sort | semaphorin3a-inhibitor ameliorates doxorubicin-induced podocyte injury |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312798/ https://www.ncbi.nlm.nih.gov/pubmed/32521824 http://dx.doi.org/10.3390/ijms21114099 |
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