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dc.contributor.authorZhou, Kailiang
dc.contributor.authorZheng, Zhilong
dc.contributor.authorLi, Yao
dc.contributor.authorHan, Wen
dc.contributor.authorZhang, Jing
dc.contributor.authorMao, Yuqin
dc.contributor.authorChen, Huanwen
dc.contributor.authorZhang, Wanying
dc.contributor.authorLiu, Mi
dc.contributor.authorXie, Ling
dc.contributor.authorZhang, Hongyu
dc.contributor.authorXu, Huazi
dc.contributor.authorXiao, Jian
dc.date.accessioned2020-09-01T16:19:11Z
dc.date.available2020-09-01T16:19:11Z
dc.date.issued2020-07-23
dc.identifier.urihttp://hdl.handle.net/10713/13609
dc.description.abstractBackground and Aim: Increasing evidence suggests that spinal cord injury (SCI)-induced defects in autophagic flux may contribute to an impaired ability for neurological repair following injury. Transcription factor E3 (TFE3) plays a crucial role in oxidative metabolism, lysosomal homeostasis, and autophagy induction. Here, we investigated the role of TFE3 in modulating autophagy following SCI and explored its impact on neurological recovery. Methods: Histological analysis via HE, Nissl and Mason staining, survival rate analysis, and behavioral testing via BMS and footprint analysis were used to determine functional recovery after SCI. Quantitative real-time polymerase chain reaction, Western blotting, immunofluorescence, TUNEL staining, enzyme-linked immunosorbent assays, and immunoprecipitation were applied to examine levels of autophagy flux, ER-stress-induced apoptosis, oxidative stress, and AMPK related signaling pathways. In vitro studies using PC12 cells were performed to discern the relationship between ROS accumulation and autophagy flux blockade. Results: Our results showed that in SCI, defects in autophagy flux contributes to ER stress, leading to neuronal death. Furthermore, SCI enhances the production of reactive oxygen species (ROS) that induce lysosomal dysfunction to impair autophagy flux. We also showed that TFE3 levels are inversely correlated with ROS levels, and increased TFE3 levels can lead to improved outcomes. Finally, we showed that activation of TFE3 after SCI is partly regulated by AMPK-mTOR and AMPK-SKP2-CARM1 signaling pathways. Conclusions: TFE3 is an important regulator in ROS-mediated autophagy dysfunction following SCI, and TFE3 may serve as a promising target for developing treatments for SCI.en_US
dc.description.urihttps://doi.org/10.7150/thno.46566en_US
dc.language.isoen_USen_US
dc.publisherIvyspring International Publisheren_US
dc.relation.ispartofTheranosticsen_US
dc.rights© The author(s).en_US
dc.subjectAMPK signaling pathwaysen_US
dc.subjectAutophagyen_US
dc.subjectER stress-induced apoptosisen_US
dc.subjectSpinal cord injuryen_US
dc.subjectTFE3en_US
dc.titleTFE3, a potential therapeutic target for Spinal Cord Injury via augmenting autophagy flux and alleviating ER stressen_US
dc.typeArticleen_US
dc.identifier.doi10.7150/thno.46566
dc.identifier.pmid32802192
dc.source.volume10
dc.source.issue20
dc.source.beginpage9280
dc.source.endpage9302
dc.source.countryAustralia


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