Expression profiling of long noncoding RNAs and the dynamic changes of lncRNA-NR024118 and Cdkn1c in angiotensin II-treated cardiac fibroblasts

Int J Clin Exp Pathol. 2014 Mar 15;7(4):1325-36. eCollection 2014.

Abstract

A growing body of evidence shows that long non-coding RNAs (lncRNAs) are involved in multiple human diseases than previously realized. However, no information is available now about lncRNAs in cardiac fibroblasts. The expression profile of lncRNAs was analyzed in Ang II-treated cardiac fibroblasts using lncRNAs arrays. The analysis showed that 282 of 4376 detected lncRNAs demonstrated >2-fold differential expression in response to the treatment with Ang II (100 nm) for 24 h. Among of them, 22 lncRNAs showed a greater than 4-fold changes. Meanwhile, Ang II also induced a widely expression changes in protein-coding genes in cardiac fibroblasts. Quantitative real time PCR confirmed the changes of six lncRNAs (AF159100, BC086588, MRNR026574, MRAK134679, NR024118, AX765700) and mRNAs (IL6, RGS2, PRG4, TIMP1, Cdkn1c, TIMP3, Col I, Col III and Fibronectin) in cardiac fibroblasts. Bioinformatic analysis indicated the process of cell proliferation. Further studies revealed that the down-regulating of Ang II on the expression of lncRNA-NR024118 was time-dependent, that the level of NR024118 was lowest at 24 h and back at 48 h. Ang II also dynamically down regulated the expression of Cdkn1c in cardiac fibroblasts. Ang II at a range from 10(-9) M to 10(-6) M induced a decrease of NR024118 and Cdkn1c in cardiac fibroblasts. In conclusion, the expression profile of lncRNAs was significantly altered in the Ang II-treated cardiac fibroblasts and Ang II dynamically regulated the expression of lncRNA-NR024118 and Cdkn1c in cardiac fibroblasts, indicating the potential role of NR024118 in cardiac fibroblasts.

Keywords: Angiotensin Π; cardiac fibroblasts; long non-coding RNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / pharmacology*
  • Animals
  • Cells, Cultured
  • Cyclin-Dependent Kinase Inhibitor p57 / genetics
  • Cyclin-Dependent Kinase Inhibitor p57 / metabolism*
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Gene Expression Profiling*
  • Gene Expression Regulation / drug effects*
  • Male
  • Microarray Analysis
  • Models, Animal
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors

Substances

  • Cyclin-Dependent Kinase Inhibitor p57
  • NR024118 long noncoding RNA, human
  • RNA, Long Noncoding
  • RNA, Messenger
  • Angiotensin II