Semaphorin3A-Inhibitor Ameliorates Doxorubicin-Induced Podocyte Injury.

International Journal of Molecular Sciences
Yizhen SangJun Wada

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 leve...Continue Reading

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Citations

Dec 31, 2020·International Journal of Molecular Sciences·Kenji TsujiJun Wada
Nov 9, 2021·American Journal of Physiology. Renal Physiology·Yizhen SangJun Wada
Jan 16, 2022·Journal of the American Society of Nephrology : JASN·Julie BejoyLauren E Woodard

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Methods Mentioned

BETA
light microscopy
Electrophoresis
immunoprecipitation assay
protein Assay
PCR
biopsies
enzyme-linked immunosorbent assay

Software Mentioned

JMP
GraphPad
GraphPad Prism5
ImageJ

Related Concepts

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Apoptosis

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