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Nature子刊:东南大学巢杰研究组发表矽肺纤维化研究论文

摘要 : 2017年12月13日,国际学术权威刊物自然出版集团旗下子刊《Cell Death & Disease》杂志在线发表了东南大学医学院巢杰教授课题组的一篇研究论文

2017年12月13日,国际学术权威刊物自然出版集团旗下子刊《Cell Death & Disease》杂志在线发表了东南大学医学院巢杰教授课题组的一篇研究论文,论文题为“circHIPK2-mediated σ-1R promotes endoplasmic reticulum stress in human pulmonary fibroblasts exposed to silica”。曹周利同学为本文第一作者,巢杰教授为论文通讯作者。

研究探讨了σ-1R是否能够通过内质网应激来参与下游细胞的增殖与分化,并且探讨了circRNA是否能够通过对σ-1R的调控来调节矽肺纤维化的进程,以期为临床诊断及治疗提供靶点。σ-1R对于细胞的调控作用多在中枢系统中报道,但其在矽肺的发生发展中扮演的角色还不清楚。本研究关注未折叠蛋白反应能够作为适应性反应来缓解内质网应激反应和恢复内质网稳态,并重点研究了矽肺发生发展中的效应细胞——人肺成纤维细胞,结果表明σ-1R可能经内质网应激反应促进矽肺纤维化的发生发展。

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原文链接:

circHIPK2-mediated σ-1R promotes endoplasmic reticulum stress in human pulmonary fibroblasts exposed to silica

原文摘要:

Mutation is the source of genetic variation and fuels biological evolution. Many mutations first arise as DNA replication errors. These errors subsequently evade correction by cellular DNA repair, for example, by the well-known DNA mismatch repair (MMR) mechanism. Here, we determine the genome-wide effects of MMR on mutation. We first identify almost 9000 mutations accumulated over five generations in eight MMR-deficient mutation accumulation (MA) lines of the model plant species, Arabidopsis thaliana. We then show that MMR deficiency greatly increases the frequency of both smaller-scale insertions and deletions (indels) and of single-nucleotide variant (SNV) mutations. Most indels involve A or T nucleotides and occur preferentially in homopolymeric (poly A or poly T) genomic stretches. In addition, we find that the likelihood of occurrence of indels in homopolymeric stretches is strongly related to stretch length, and that this relationship causes ultrahigh localized mutation rates in specific homopolymeric stretch regions. For SNVs, we show that MMR deficiency both increases their frequency and changes their molecular mutational spectrum, causing further enhancement of the GC to AT bias characteristic of organisms with normal MMR function. Our final genome-wide analyses show that MMR deficiency disproportionately increases the numbers of SNVs in genes, rather than in nongenic regions of the genome. This latter observation indicates that MMR preferentially protects genes from mutation and has important consequences for understanding the evolution of genomes during both natural selection and human tumor growth.

来源: Cell Death & Disease 浏览次数:0

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