Mandible exosomal ssc-mir-133b regulates tooth development in miniature swine via endogenous apoptosis.

Mandible exosomal ssc-mir-133b regulates tooth development in miniature swine via endogenous apoptosis.
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下颌骨外泌体 ssc-mir-133b 通过内源性细胞凋亡调节小型猪的牙齿发育

DOI:
10.1038/s41413-018-0028-5
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发表时间:
2018
期刊:
影响因子:
12.7
通讯作者:
Wang S
Wang S
中科院分区:
医学1区
文献类型:
--
作者:
Li Y;Wang X;Ren J;Wu X;Li G;Fan Z;Zhang C;Li A;Wang S

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不同器官之间的信号转导在人体正常发育中起着至关重要的作用。外泌体作为信号交流的重要媒介,可以将microrna (mirna)等重要信息从供体传递到受体。众所周知,mirna可以微调多种生物过程,包括颌面发育;然而,潜在的机制在很大程度上仍然未知。在本研究中,发现一种微型猪颌面特异性miRNA ssc-mir-133b的表达导致了短暂的细胞凋亡。ssc-mir-133b的上调导致颌面部原代牙间充质细胞大量凋亡。细胞白血病髓系1 (Mcl-1)被证实是功能靶点,在牙齿发育过程中引发内源性线粒体相关凋亡过程的进一步下游激活。更重要的是,下颌骨外泌体负责初始凋亡信号。一项动物研究表明,ssc-mir-133b的异位表达导致裸鼠皮下移植12周后牙齿形成失败。牙胚发育异常,缺乏来自下颌骨必不可少的外泌体信号。
Signal transduction between different organs is crucial in the normal development of the human body. As an important medium for signal communication, exosomes can transfer important information, such as microRNAs (miRNAs), from donors to receptors. MiRNAs are known to fine-tune a variety of biological processes, including maxillofacial development; however, the underlying mechanism remains largely unknown. In the present study, transient apoptosis was found to be due to the expression of a miniature swine maxillofacial-specific miRNA, ssc-mir-133b. Upregulation of ssc-mir-133b resulted in robust apoptosis in primary dental mesenchymal cells in the maxillofacial region. Cell leukemia myeloid 1 (Mcl-1) was verified as the functional target, which triggered further downstream activation of endogenous mitochondria-related apoptotic processes during tooth development. More importantly, mandible exosomes were responsible for the initial apoptosis signal. An animal study demonstrated that ectopic expression of ssc-mir-133b resulted in failed tooth formation after 12 weeks of subcutaneous transplantation in nude mice. The tooth germ developed abnormally without the indispensable exosomal signals from the mandible.
DOI: 10.1111/eos.12056
发表时间: 2013-08-01
影响因子: 1.9
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期刊: ONCOGENE
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DOI: 10.1101/gad.12.16.2636
发表时间: 1998-08-15
影响因子: 10.5
作者:
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通讯作者: Sharpe, PT