Long non-coding RNA-SRA promotes neointimal hyperplasia and vascular smooth muscle cells proliferation via MEK-ERK-CREB pathway.

Abstract

Long noncoding RNA-steroid receptor RNA activator (LncRNA-SRA) is transcribed from a class of noncoding genes, and plays a critical role in regulating cell proliferation. However, the effect of lncRNA-SRA remains unclear in vascular proliferative diseases. In the present study, we overexpressed lncRNA-SRA in vitro, then investigated the biological consequences. A vascular damage mice model was constructed by performing femoral artery wire injury. LncRNA-SRA was overexpressed in the injured arteries, and significantly promoted the expression of ki67, thereby caused an overall increase in neointima formation. LncRNA-SRA overexpression led to the proliferation and migration of vascular smooth muscle cells (VSMCs). By stimulating the phosphorylation of MEK, ERK and CREB (cyclic nucleotide responsive element binding protein), lncRNA-SRA promoted VSMC proliferation. Meanwhile, these effects were blocked by the MEK inhibitor U0126. Therefore, lncRNA-SRA promoted VSMC proliferation by activating the MEK-ERK-CREB pathway. LncRNA-SRA could be a promising therapeutic target in vascular diseases characterized by neointimal hyperplasia.

• Authors: Chan-Juan Zhang, Chan Liu, Yu-Xiang Wang, Neng Zhu, Zhe-Yu Hu, Duan-Fang Liao, Li Qin
• Journal: Vascular pharmacology (Vascul Pharmacol) Vol. 116 Pg. 16-23 (05 2019) ISSN: 1879-3649 [Electronic] United States
• PMID: 30822571 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Creb1 protein, mouse
• Cyclic AMP Response Element-Binding Protein
• RNA, Long Noncoding
• steroid receptor RNA activator
• Extracellular Signal-Regulated MAP Kinases
• MAP Kinase Kinase Kinases

Topics

• Animals
• Cell Proliferation
• Cells, Cultured
• Cyclic AMP Response Element-Binding Protein (metabolism)
• Disease Models, Animal
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Femoral Artery (enzymology, injuries, pathology)
• Hyperplasia
• MAP Kinase Kinase Kinases (metabolism)
• Male
• Mice, Inbred C57BL
• Muscle, Smooth, Vascular (enzymology, injuries, pathology)
• Myocytes, Smooth Muscle (enzymology, pathology)
• Neointima
• Phosphorylation
• RNA, Long Noncoding (genetics, metabolism)
• Signal Transduction
• Vascular System Injuries (enzymology, genetics, pathology)