LncRNA PSR Regulates Vascular Remodeling Through Encoding a Novel Protein Arteridin

Area of Science:

• Cardiovascular Biology
• Molecular Mechanisms of Disease
• Gene Regulation

Background:

• Vascular smooth muscle cell (VSMC) phenotype switching is crucial in cardiovascular diseases.
• Long noncoding RNAs (lncRNAs) are increasingly recognized for producing functional peptides.
• The role of lncRNAs in VSMC phenotype switching requires further elucidation.

Purpose of the Study:

• To investigate the function and mechanism of a VSMC-enriched lncRNA and its encoded peptide.
• To understand their role in VSMC phenotype switching and vascular remodeling.

Main Methods:

• Identification and characterization of a novel VSMC-enriched gene, phenotype switching regulator (PSR).
• Demonstration of lncPSR transcript encoding a protein, arteridin.
• Assessment of arteridin and lncPSR function in VSMCs and in vivo models of vascular remodeling.
• Investigation of the interaction with Y-box binding protein 1 (YBX1).

Main Results:

• PSR is upregulated during vascular remodeling; lncPSR encodes arteridin.
• Both lncPSR and arteridin induce VSMC phenotype switching.
• Arteridin and lncPSR regulate gene expression via YBX1 interaction and nuclear translocation.
• Loss of PSR or arteridin attenuates vascular remodeling in injury and hypertension models.

Conclusions:

• PSR, lncPSR, and arteridin form a novel regulatory circuit in VSMC phenotype switching.
• This circuit involves coordinated regulation through YBX1.
• lncPSR/arteridin represent potential therapeutic targets for vascular remodeling-related diseases.