Losartan reverses the down-expression of long noncoding RNA-NR024118 and Cdkn1c induced by angiotensin II in adult rat cardiac fibroblasts

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.

RésuméAngiotensin II (Ang II) joue un rôle central dans la pathogénie de fibrose cardiaque et longtemps le noncodage d’ARN (lncRNAs) a révélé être impliqué dans des maladies humaines. Les rôles de récepteurs d’Ang II (AT1 et AT2) ont été controversés. Nos études précédentes ont révélé qu’Ang II dynamiquement en bas mesuré l’expression de lncRNA-NR024118 et Cdkn1c des fibroblastes cardiaques chez le rat adulte. Cependant, jusqu’ici, si la diminution de lncRNA-NR024118 et Cdkn1c induit par Ang II est obtenue par médiation par AT1 ou AT2 n’a jamais été illustrée. Pour révéler que le sous-type de récepteurs d’Ang II on obtient par médiation la diminution de lncRNA-NR024118 et Cdkn1c induit par Ang II, nous avons étudié l’expression de NR024118 et Cdkn1c avec des bloqueurs de récepteur différents dans Ang II–treated des fibroblastes cardiaques chez le rat adulte. Voici le résultat de cette étude.