A micro RNA processing defect in rapidly progressing idiopathic pulmonary fibrosis.
A micro RNA processing defect in rapidly progressing idiopathic pulmonary fibrosis.
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在快速发展的特发性肺纤维化中的微RNA处理缺陷。
DOI：
10.1371/journal.pone.0021253
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Hogaboam CM
中科院分区：
文献类型：
--
作者：
Oak SR;Murray L;Herath A;Sleeman M;Anderson I;Joshi AD;Coelho AL;Flaherty KR;Toews GB;Knight D;Martinez FJ;Hogaboam CM
特发性肺纤维化从诊断时起表现出不同的进展，但对不同进展率的分子基础知之甚少。本研究的目的是确定差异miRNA表达是否可以为IPF的快速与缓慢进展形式提供一种解释。从IPF患者的手术肺活检中分离miRNA和mRNA，这些患者在诊断后的第一年内具有临床记录的快速或缓慢病程。使用含有人类基因组中88种最丰富的miRNA的定量PCR miRNA阵列来分析来自9名快速进展的IPF患者、6名缓慢进展的IPF患者和10名正常肺活检组织的肺活检组织。使用这种方法，与正常活检相比，快速活检中有11种miRNA显著增加，36种显著减少。与正常肺组织相比，缓慢进行性活检显示4个显著增加的miRNA和36个显著减少的miRNA。在IPF中存在的具有经验证的mRNA靶点的miRNA中，有对上皮-间充质转化（EMT）具有调节作用的miRNA。与慢速IPF肺活检相比，快速IPF肺活检中5种miRNA（miR-302 c、miR-423- 5 p、miR-210、miR-376 c和miR-185）显著增加。对快速活检组织和从相同活检组织生长的成纤维细胞的额外分析显示，AGO 1和AGO 2（miRNA加工RISC复合物的基本组分）的表达低于缓慢或正常肺活检组织和成纤维细胞。这些发现表明IPF的发生和/或临床进展可能是异常miRNA加工的结果。
Idiopathic pulmonary fibrosis exhibits differential progression from the time of diagnosis but the molecular basis for varying progression rates is poorly understood. The aim of the present study was to ascertain whether differential miRNA expression might provide one explanation for rapidly versus slowly progressing forms of IPF. miRNA and mRNA were isolated from surgical lung biopsies from IPF patients with a clinically documented rapid or slow course of disease over the first year after diagnosis. A quantitative PCR miRNA array containing 88 of the most abundant miRNA in the human genome was used to profile lung biopsies from 9 patients with rapidly progressing IPF, 6 patients with slowly progressing IPF, and 10 normal lung biopsies. Using this approach, 11 miRNA were significantly increased and 36 were significantly decreased in rapid biopsies compared with normal biopsies. Slowly progressive biopsies exhibited 4 significantly increased miRNA and 36 significantly decreased miRNA compared with normal lung. Among the miRNA present in IPF with validated mRNA targets were those with regulatory effects on epithelial-mesenchymal transition (EMT). Five miRNA (miR-302c, miR-423-5p, miR-210, miR-376c, and miR-185) were significantly increased in rapid compared with slow IPF lung biopsies. Additional analyses of rapid biopsies and fibroblasts grown from the same biopsies revealed that the expression of AGO1 and AGO2 (essential components of the miRNA processing RISC complex) were lower compared with either slow or normal lung biopsies and fibroblasts. These findings suggest that the development and/or clinical progression of IPF might be the consequence of aberrant miRNA processing.
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影响因子：
64.8
作者：
Chendrimada, TP;Gregory, RI;Shiekhattar, R
通讯作者：
Shiekhattar, R
影响因子：
10
作者：
Flaherty, KR;Thwaite, EL;Martinez, FJ
通讯作者：
Martinez, FJ
DOI：
10.1126/science.1174334
发表时间：
2009-08-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hill DA;Ivanovich J;Priest JR;Gurnett CA;Dehner LP;Desruisseau D;Jarzembowski JA;Wikenheiser-Brokamp KA;Suarez BK;Whelan AJ;Williams G;Bracamontes D;Messinger Y;Goodfellow PJ
通讯作者：
Goodfellow PJ
DOI：
10.1164/rccm.200402-147oc
发表时间：
2004-10-15
影响因子：
24.7
作者：
Flaherty, KR;King, TE;Martinez, FJ
通讯作者：
Martinez, FJ
DOI：
10.1073/pnas.0510839103
发表时间：
2006-02-14
影响因子：
11.1
作者：
Harris, KS;Zhang, Z;Sun, X
通讯作者：
Sun, X