2012年9月14日，心血管基礎研究的最高專業(yè)期刊Circulation Research以“超快通訊（Ultra-rapid Communication）”的優(yōu)先形式發(fā)表了我院王世強教授實驗室與北醫(yī)三院,、中科院遺傳發(fā)育所等單位的合作研究成果：miR-24 抑制junctophilin-2(JP2)的表達導致心肌細胞興奮收縮耦聯(lián)減弱,。該期Circulation Research同時配發(fā)了一篇述評,，高度評價該發(fā)現(xiàn)揭示了心力衰竭病理過程的關鍵調控機制。
心力衰竭是多種心臟病的最后階段,，是威脅人類健康和生命的重大疾病之一,。2007年以來，王世強教授實驗室與北醫(yī)三院合作在PLoS Biology和Cardiovascular Research等重要期刊發(fā)表系列論文,，證明細胞膜鈣通道與肌質網鈣釋放通道的耦聯(lián)效率在心力衰竭中進行性衰退,，且其關鍵原因是錨定兩分子所在膜結構的JP2表達下降，有關成果被Nature Reviews Drug Discovery選為亮點,。在上述研究基礎上,，該實驗室繼續(xù)尋找心力衰竭過程中JP2表達量下降的原因，發(fā)現(xiàn)JP2基因的非編碼區(qū)有兩個miR-24結合位點,，且心力衰竭細胞中miR-24表達量顯著上升,。他們由此系統(tǒng)地證明，miR-24上調抑制了JP2的表達,，從而導致心肌細胞興奮收縮耦聯(lián)的結構重塑和效率下降,。
心血管領域大量研究證明，交感神經遞質,、血管緊張素等導致心肌肥厚和心力衰竭的體液因子通過復雜的信號轉導啟動了NFAT等轉錄因子,，但這些轉錄因子的激活如何導致心臟收縮減弱一直未能闡明。由于miR-24位于NFAT調控的microRNA簇內,，上述發(fā)現(xiàn)第一次將上游信號轉導的途徑與下游收縮功能的減弱聯(lián)系起來,。Circulation Research配發(fā)的述評指出，該發(fā)現(xiàn)為未來探索心力衰竭的治療對策提供了新思路。（生物谷Bioon.com）
doi: 10.1161/CIRCRESAHA.112.277418
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Mir-24 Regulates Junctophilin-2 Expression in Cardiomyocytes
Ming Xu*, Hao-Di Wu*, Rong-Chang Li*, Hai-Bo Zhang*, Meng Wang*, Jin Tao, Xin-Heng Feng, Yun-Bo Guo, Su-Fang Li, Shao-Ting Lai, Peng Zhou, Lin-Lin Li, Hua-Qian Yang, Guan-Zheng Luo, Yan Bai, Jianzhong J. Xi, Wei Gao, Qi-De Han, You-Yi Zhang, Xiu-Jie Wang, Xu Meng, Shi-Qiang Wang
Rationale: Failing cardiomyocytes exhibit decreased efficiency of excitation-contraction (E-C) coupling. The downregulation of junctophilin-2 (JP2), a protein anchoring the sarcoplasmic reticulum to T-tubules, has been identified as a major mechanism underlying the defective E-C coupling. However, the regulatory mechanism of JP2 remains unknown. Objective: To determine whether microRNAs regulate JP2 expression. Methods and Results: Bioinformatic analysis predicted 2 potential binding sites of miR-24 in the 3′-untranslated regions of JP2 mRNA. Luciferase assays confirmed that miR-24 suppressed JP2 expression by binding to either of these sites. In the aortic stenosis model, miR-24 was upregulated in failing cardiomyocytes. Adenovirus-directed overexpression of miR-24 in cardiomyocytes decreased JP2 expression and reduced Ca2+ transient amplitude and E-C coupling gain. Conclusions: MiR-24–mediated suppression of JP2 expression provides a novel molecular mechanism for E-C coupling regulation in heart cells and suggests a new target against heart failure.
