Format

Send to

Choose Destination
Am J Respir Cell Mol Biol. 2018 Feb;58(2):181-193. doi: 10.1165/rcmb.2017-0111OC.

The Long Noncoding RNA LnRPT Is Regulated by PDGF-BB and Modulates the Proliferation of Pulmonary Artery Smooth Muscle Cells.

Chen J1,2,3, Guo J1, Cui X1,2, Dai Y4, Tang Z1,2, Qu J3, Raj JU5, Hu Q6,7, Gou D1,2.

Author information

1
1 Shenzhen Key Laboratory of Microbial Genetic Engineering.
2
2 Shenzhen Key Laboratory of Marine Bioresource and Eco-environmental Science, College of Life Sciences, and.
3
3 Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, China.
4
4 Key Laboratory of Systems Biology, Chinese Academy of Science, Shanghai Institute for Biological Sciences, Shanghai, China.
5
5 Department of Pediatrics, University of Illinois at Chicago, Chicago, Illinois; and.
6
6 Department of Pathophysiology and.
7
7 Key Laboratory of Pulmonary Diseases of Ministry of Health, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Abstract

Pulmonary artery hypertension (PAH) is a rare and fatal disorder that involves extensive remodeling of the pulmonary arteries mediated by hyperproliferation of pulmonary artery smooth muscle cells (PASMCs). Aberrant platelet-derived growth factor (PDGF) activity can lead to hyperproliferation of PASMCs; however, little is known about the role of long noncoding RNA (lncRNA) in this process. Using RNA sequencing, we identified 725 lncRNAs in rat PASMCs, 95 of which were expressed differentially in response to PDGF-BB treatment. Depletion of four lncRNAs affected the proliferation of rat PASMCs as measured by 5-ethynyl-2'-deoxyuridine incorporation assay. Among these, one lncRNA, named LnRPT (lncRNA regulated by PDGF and transforming growth factor β), was found to be the most potent in promoting the proliferation of PASMCs when knocked down. In contrast, proliferation of PASMCs was repressed when LnRPT was overexpressed. Mechanistically, LnRPT inhibited the expression of two genes involved in the Notch signaling pathway (notch3 and jag1) as well as the cell-cycle-regulating gene ccna2. In addition, downregulation of LnRPT induced by PDGF-BB was abrogated when phosphatidylinositol 3'-kinase activity was inhibited with pictilisib. Downregulation of LnRPT was also observed in the pulmonary arteries of rats with monocrotaline-induced PAH. This study provides novel insights into the effects of PDGF-BB on lncRNA expression in PASMCs, and identifies one lncRNA, LnRPT, that plays a role in PAH development as a regulator of PASMC proliferation by mediating the Notch signaling pathway and cell cycle.

KEYWORDS:

PDGF-BB; long noncoding RNA; proliferation; pulmonary artery hypertension; pulmonary artery smooth muscle cell

PMID:
28915060
DOI:
10.1165/rcmb.2017-0111OC
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center