Key result
Depletion of the long noncoding RNA LnRPT promoted the proliferation of rat pulmonary artery smooth muscle cells, while its overexpression repressed proliferation.
Why the study?
Does the long noncoding RNA LnRPT modulate the proliferation of pulmonary artery smooth muscle cells in response to PDGF-BB?
Does the long noncoding RNA LnRPT modulate the proliferation of pulmonary artery smooth muscle cells in response to PDGF-BB?
The lncRNA LnRPT regulates pulmonary artery smooth muscle cell proliferation via the Notch signaling pathway and cell cycle, offering novel mechanistic insights into PAH development.
No immediate clinical implications; leaves open lncRNA roles in PDGF-driven PASMC proliferation in PAH.
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.
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Chen et al. (2017) studied Pulmonary artery hypertension. LnRPT knockdown and overexpression was evaluated on Proliferation of pulmonary artery smooth muscle cells. Depletion of the long noncoding RNA LnRPT promoted the proliferation of rat pulmonary artery smooth muscle cells, while its overexpression repressed proliferation.
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