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

Pathol Biol (Paris). 2015 Jun;63(3):122-5. doi: 10.1016/j.patbio.2015.04.001. Epub 2015 May 12.

Abstract

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.

Keywords: AT1; Angiotensin II; Cardiac fibroblasts; Cdkn1c; Fibroblastes cardiaques; LncRNA-NR024118; Long noncoding RNA-NR024118.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / pharmacology*
  • Angiotensin II Type 1 Receptor Blockers / pharmacology*
  • Animals
  • Cells, Cultured
  • Cyclin-Dependent Kinase Inhibitor p57 / biosynthesis*
  • Cyclin-Dependent Kinase Inhibitor p57 / genetics
  • Down-Regulation / drug effects
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Imidazoles / pharmacology
  • Losartan / pharmacology*
  • Male
  • Myocardium / cytology*
  • Pyridines / pharmacology
  • RNA, Long Noncoding / biosynthesis*
  • RNA, Long Noncoding / genetics
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Receptor, Angiotensin, Type 1 / drug effects
  • Receptor, Angiotensin, Type 1 / physiology*
  • Receptor, Angiotensin, Type 2 / drug effects

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Cyclin-Dependent Kinase Inhibitor p57
  • Imidazoles
  • NR024118 long noncoding RNA, rat
  • Pyridines
  • RNA, Long Noncoding
  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • Angiotensin II
  • PD 123319
  • Losartan