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Bone morphogenetic protein (BMP) 7 expression is regulated by the E3 ligase UBE4A in diabetic nephropathy

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机构: [1]Department of Endocrinology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China [2]Department ofTraditional Chinese Medicine, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China [3]Department ofDermatology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
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关键词: BMP7 Diabetic nephropathy E3 ligase UBE4A

摘要:
Mesangial cells played a central role in the pathophysiology of diabetic nephropathy (DN). Our goal was to evaluate the molecular mechanism that regulates loss of BMP7 protein expression in DN. The mRNA and protein levels of BMP7 or UBE4A were detected using qRT-PCR and Western blot respectively. Mass spectrometry and co-immunoprecipitation were used to explore the E3 ligase which regulated BMP7 post-translationally. We initially confirmed that BMP7 protein, but not mRNA, is downregulated when cultured under high glucose mimicking DN conditions, which was rescued by MG-132 treatment. Proteomic analysis of NRK-52E cells ± MG-132 revealed a list of ubiquitin ligases associated with BMP7. Knockdown of the ubiquitin ligase UBE4A stabilized BMP7 expression in NRK-52E cells grown under high glucose conditions. Concurrent overexpression experiments confirmed that UBE4A is the ubiquitin ligase that degrades BMP7. Co-immunoprecipitation analysis confirmed that BMP7 and UBE4A interact. BMP7 expression in DN is regulated by post-translational mechanism. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.

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出版当年[2019]版:
大类 | 4 区 医学
小类 | 4 区 内分泌学与代谢 4 区 生理学
最新[2025]版:
大类 | 4 区 医学
小类 | 4 区 内分泌学与代谢 4 区 生理学
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出版当年[2018]版:
Q3 PHYSIOLOGY Q4 ENDOCRINOLOGY & METABOLISM
最新[2023]版:
Q2 PHYSIOLOGY Q3 ENDOCRINOLOGY & METABOLISM

影响因子: 最新[2023版] 最新五年平均 出版当年[2018版] 出版当年五年平均 出版前一年[2017版] 出版后一年[2019版]

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第一作者机构: [1]Department of Endocrinology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China
通讯作者:
通讯机构: [3]Department ofDermatology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China [*1]Department of Dermatology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, No.56, Nanlishi Road, Beijing 100045, China
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