LncRNA MFRL regulates the phenotypic switch of vascular smooth muscle cells to attenuate arterial remodeling by encoding a novel micropeptide MFRLP

LncRNA MFRL 通过编码新型微肽 MFRLP 来调节血管平滑肌细胞的表型转换以减轻动脉重塑

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作者:Xiaocong Liu, Siyu Chen, Wei Luo, Chen Yu, Shaohua Yan, Li Lei, Shifeng Qiu, Xinxin Lin, Ting Feng, Jinglin Shi, Qiuxia Zhang, Hongbin Liang, Xuewei Liu, Alex Pui-Wai Lee, Lei Zheng, Xinlu Zhang, Jiancheng Xiu

Background

Arterial remodeling is a common pathophysiological change in the pathogenesis of cardiovascular diseases in which the phenotypic switch of vascular smooth muscle cells (VSMC) plays an important role. Recently, an increasing number of long non-coding RNAs(lncRNAs) have been shown to encode micropeptides that play biological roles and have great clinical transformation potential. However, the role of micropeptides encoded by lncRNAs in arterial remodeling has not been well studied and requires further exploration.

Conclusions

LncRNA MFRL encodes the micropeptide MFRLP, which interacts with mitochondrial cytochrome b to inhibit the VSMC switch from contractile to synthetic phenotype and improve arterial remodeling.

Results

Through bioinformatic analysis and experimental verification, we found that a new lncRNA, the mitochondrial function-related lncRNA (MFRL), encodes a 64-amino acid micropeptide, MFRLP. MFRL and MFRLP play important roles in the phenotypic switch of VSMC. Further experiments showed that MFRLP interacts with mitochondrial cytochrome b to reduce accumulation of reactive oxygen species, suppress mitophagy and inhibit the VSMC switch from contractile to synthetic phenotype. Conclusions: LncRNA MFRL encodes the micropeptide MFRLP, which interacts with mitochondrial cytochrome b to inhibit the VSMC switch from contractile to synthetic phenotype and improve arterial remodeling.

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