MicroRNA mimicry blocks pulmonary fibrosis.
MicroRNA mimicry blocks pulmonary fibrosis.
复制标题
DOI：
10.15252/emmm.201303604
复制
发表时间：
2014-10
影响因子：
11.1
通讯作者：
van Rooij E
中科院分区：
文献类型：
--
作者：
Montgomery RL;Yu G;Latimer PA;Stack C;Robinson K;Dalby CM;Kaminski N;van Rooij E
在过去的十年中，人们对microRNA （miRNA）疗法产生了极大的热情。令人兴奋的部分原因是一个miRNA经常调节许多相关的mrna。因此，单个miRNA的调节允许平行调节涉及特定疾病的多个基因。虽然许多研究表明使用miRNA抑制剂具有治疗效果，但恢复或增加miRNA功能的努力一直滞后。miR-29家族因其在组织纤维化中的明确功能而备受关注。这个富含成纤维细胞的miRNA家族在纤维化疾病中下调，诱导许多细胞外基质基因的协同增加。在这里，我们表明静脉注射合成RNA双链可以在体内增加miR-29水平数天。此外，在博莱霉素诱导的肺纤维化期间，治疗性递送这些miR-29模拟物可恢复内源性miR-29功能，从而降低胶原表达，阻断和逆转肺纤维化。我们的数据支持使用miRNA模拟物治疗性增加miRNA的可行性，并表明miR-29是治疗肺纤维化的有效治疗miRNA。
Over the last decade, great enthusiasm has evolved for microRNA (miRNA) therapeutics. Part of the excitement stems from the fact that a miRNA often regulates numerous related mRNAs. As such, modulation of a single miRNA allows for parallel regulation of multiple genes involved in a particular disease. While many studies have shown therapeutic efficacy using miRNA inhibitors, efforts to restore or increase the function of a miRNA have been lagging behind. The miR-29 family has gained a lot of attention for its clear function in tissue fibrosis. This fibroblast-enriched miRNA family is downregulated in fibrotic diseases which induces a coordinate increase of many extracellular matrix genes. Here, we show that intravenous injection of synthetic RNA duplexes can increase miR-29 levels in vivo for several days. Moreover, therapeutic delivery of these miR-29 mimics during bleomycin-induced pulmonary fibrosis restores endogenous miR-29 function whereby decreasing collagen expression and blocking and reversing pulmonary fibrosis. Our data support the feasibility of using miRNA mimics to therapeutically increase miRNAs and indicate miR-29 to be a potent therapeutic miRNA for treating pulmonary fibrosis.