微RNA（調(diào)控基因表達(dá)的小型非編碼RNA）已被發(fā)現(xiàn)在心肌細(xì)胞中表達(dá),，而且它們的異常調(diào)控與心臟病有關(guān),。Thum等人對(duì)其他心臟細(xì)胞中的微RNA會(huì)怎樣影響發(fā)病進(jìn)行了研究。他們發(fā)現(xiàn),，微RNA-21（miR-21）在小鼠心臟病模型的心臟成纖維細(xì)胞中被上調(diào),。這會(huì)激發(fā)一個(gè)信號(hào)通道，加重心臟組織的損傷程度,。當(dāng)利用一個(gè)特定的抗轉(zhuǎn)錄寡核苷酸（一個(gè)抗miR-21的antagomir）使miR-21沉默時(shí),，心臟衰竭可以防止。另外,，在心臟衰竭已經(jīng)出現(xiàn)后給小鼠施用抗miR-21藥物,，似乎可使組織損傷得到一定逆轉(zhuǎn)。這項(xiàng)工作確認(rèn)miR-21是心臟衰竭中的一個(gè)疾病目標(biāo),，并且說明微RNA具有廣泛的治療潛力,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 456, 980-984 (18 December 2008) | doi:10.1038/nature07511
MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts
Thomas Thum1,2,15, Carina Gross3,15, Jan Fiedler1,2, Thomas Fischer3, Stephan Kissler3, Markus Bussen5, Paolo Galuppo1, Steffen Just6, Wolfgang Rottbauer6, Stefan Frantz1, Mirco Castoldi7,8, Jürgen Soutschek9, Victor Koteliansky10, Andreas Rosenwald4, M. Albert Basson11, Jonathan D. Licht12, John T. R. Pena13, Sara H. Rouhanifard13, Martina U. Muckenthaler7,8, Thomas Tuschl13, Gail R. Martin5, Johann Bauersachs1 & Stefan Engelhardt3,14
1 Department of Medicine I,
2 Junior Research Group, Interdisziplin?res Zentrum für Klinische Forschung (IZKF)
3 Rudolf Virchow Center, Deutsche Forschungsgemeinschaft (DFG) Research Center for Experimental Biomedicine,
4 Institute of Pathology, University of Wuerzburg, 97080 Wuerzburg, Germany
5 Department of Anatomy, University of California, San Francisco, California 94158, USA
6 Department of Internal Medicine III,
7 Department of Pediatric Hematology, Oncology and Immunology
8 Molecular Medicine Partnership Unit, University of Heidelberg, 69120 Heidelberg, Germany
9 Regulus Therapeutics, Carlsbad, California 92008, USA
10 Alnylam Pharmaceuticals, Cambridge, Massachusetts 02142, USA
11 Department of Craniofacial Development, King's College, London SE1 9RT, UK
12 Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA
13 Laboratory of RNA Molecular Biology, Rockefeller University, New York, New York 10065, USA
14 Institute of Pharmacology and Toxicology, Technische Universitaet Muenchen (TUM), 80802 Muenchen, Germany.
15 These authors contributed equally to this work.
MicroRNAs comprise a broad class of small non-coding RNAs that control expression of complementary target messenger RNAs1, 2. Dysregulation of microRNAs by several mechanisms has been described in various disease states3, 4, 5 including cardiac disease6, 7, 8, 9, 10. Whereas previous studies of cardiac disease have focused on microRNAs that are primarily expressed in cardiomyocytes, the role of microRNAs expressed in other cell types of the heart is unclear. Here we show that microRNA-21 (miR-21, also known as Mirn21) regulates the ERK–MAP kinase signalling pathway in cardiac fibroblasts, which has impacts on global cardiac structure and function. miR-21 levels are increased selectively in fibroblasts of the failing heart, augmenting ERK–MAP kinase activity through inhibition of sprouty homologue 1 (Spry1). This mechanism regulates fibroblast survival and growth factor secretion, apparently controlling the extent of interstitial fibrosis and cardiac hypertrophy. In vivo silencing of miR-21 by a specific antagomir in a mouse pressure-overload-induced disease model reduces cardiac ERK–MAP kinase activity, inhibits interstitial fibrosis and attenuates cardiac dysfunction. These findings reveal that microRNAs can contribute to myocardial disease by an effect in cardiac fibroblasts. Our results validate miR-21 as a disease target in heart failure and establish the therapeutic efficacy of microRNA therapeutic intervention in a cardiovascular disease setting.
