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Semaphorin3A-Inhibitor Ameliorates Doxorubicin-Induced Podocyte Injury

Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(11), 4099;
Received: 19 May 2020 / Revised: 30 May 2020 / Accepted: 5 June 2020 / Published: 8 June 2020
(This article belongs to the Section Molecular Endocrinology and Metabolism)
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. View Full-Text
Keywords: semaphorin3A; podocyte; proteinuria; apoptosis; c-Jun N-terminal kinase semaphorin3A; podocyte; proteinuria; apoptosis; c-Jun N-terminal kinase
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MDPI and ACS Style

Sang, Y.; Tsuji, K.; Inoue-Torii, A.; Fukushima, K.; Kitamura, S.; Wada, J. Semaphorin3A-Inhibitor Ameliorates Doxorubicin-Induced Podocyte Injury. Int. J. Mol. Sci. 2020, 21, 4099.

AMA Style

Sang Y, Tsuji K, Inoue-Torii A, Fukushima K, Kitamura S, Wada J. Semaphorin3A-Inhibitor Ameliorates Doxorubicin-Induced Podocyte Injury. International Journal of Molecular Sciences. 2020; 21(11):4099.

Chicago/Turabian Style

Sang, Yizhen, Kenji Tsuji, Akiko Inoue-Torii, Kazuhiko Fukushima, Shinji Kitamura, and Jun Wada. 2020. "Semaphorin3A-Inhibitor Ameliorates Doxorubicin-Induced Podocyte Injury" International Journal of Molecular Sciences 21, no. 11: 4099.

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