論文

査読有り 国際誌
2020年6月8日

Semaphorin3A-Inhibitor Ameliorates Doxorubicin-Induced Podocyte Injury.

International journal of molecular sciences
  • Yizhen Sang
  • ,
  • Kenji Tsuji
  • ,
  • Akiko Inoue-Torii
  • ,
  • Kazuhiko Fukushima
  • ,
  • Shinji Kitamura
  • ,
  • Jun Wada

21
11
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.3390/ijms21114099

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.

リンク情報
DOI
https://doi.org/10.3390/ijms21114099
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32521824
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312798
ID情報
  • DOI : 10.3390/ijms21114099
  • PubMed ID : 32521824
  • PubMed Central 記事ID : PMC7312798

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