Jiang X, Zhang F, Ning Q
Department of Biochemistry and Molecular Biology, School of Medicine, Xi'an Jiaotong University, 76, Yanta West Road, Xi'an, 710061 Shaanxi, China.
Department of Biochemistry and Molecular Biology, School of Medicine, Xi'an Jiaotong University, 76, Yanta West Road, Xi'an, 710061 Shaanxi, China.
Pathol Biol (Paris). 2015 Jun;63(3):122-5. doi: 10.1016/j.patbio.2015.04.001. Epub 2015 May 12.
Angiotensin II (Ang II) plays a pivotal role in the pathogenesis of cardiac fibrosis and long noncoding RNAs (lncRNAs) have been found to be involved in human diseases. The roles of Ang II receptors (AT1 and AT2) have been controversial. Our previous studies revealed that Ang II dynamically down-regulated the expression of lncRNA-NR024118 and Cdkn1c in adult rat cardiac fibroblasts. However, up to now, whether the decrease of lncRNA-NR024118 and Cdkn1c induced by Ang II is mediated by AT1 or AT2 has never been illustrated. In order to reveal which subtype of Ang II receptors mediate the decrease of lncRNA-NR024118 and Cdkn1c induced by Ang II, we studied the expression of NR024118 and Cdkn1c with different receptor blockers in Ang II-treated adult rat cardiac fibroblasts. In this study, we found that losartan (AT1 blocker) nearly completely reversed the decrease of lncRNA-NR024118 and partly reversed the decrease of Cdkn1c induced by Ang II in adult rat cardiac fibroblasts, while AT2 blocker (PD123319) did not show effect to the level of lncRNA-NR024118 and Cdkn1c. In conclusion, our current studies showed that the decrease of lncRNA-NR024118 and Cdkn1c induced by Ang II is mediated by AT1 receptor-dependent not AT2 receptor-dependent, which is helpful to understand the molecular mechanism of Ang II receptors in adult rat cardiac fibroblasts.
血管紧张素II（Ang II）在心脏纤维化的发病机制中起关键作用，并且已发现长链非编码RNA（lncRNAs）参与人类疾病。血管紧张素II受体（AT1和AT2）的作用一直存在争议。我们之前的研究表明，Ang II可动态下调成年大鼠心脏成纤维细胞中lncRNA-NR024118和Cdkn1c的表达。然而，截至目前，Ang II诱导的lncRNA-NR024118和Cdkn1c的减少是由AT1还是AT2介导尚未阐明。为了揭示Ang II受体的哪种亚型介导Ang II诱导的lncRNA-NR024118和Cdkn1c的减少，我们在Ang II处理的成年大鼠心脏成纤维细胞中使用不同的受体阻滞剂研究了NR024118和Cdkn1c的表达。在本研究中，我们发现氯沙坦（AT1阻滞剂）几乎完全逆转了成年大鼠心脏成纤维细胞中Ang II诱导的lncRNA-NR024118的减少，并部分逆转了Cdkn1c的减少，而AT2阻滞剂（PD123319）对lncRNA-NR024118和Cdkn1c的水平没有影响。总之，我们目前的研究表明，Ang II诱导的lncRNA-NR024118和Cdkn1c的减少是由AT1受体依赖性介导而非AT2受体依赖性介导，这有助于理解成年大鼠心脏成纤维细胞中Ang II受体的分子机制。
