In:
Cellular and Molecular Life Sciences, Springer Science and Business Media LLC, Vol. 80, No. 5 ( 2023-05)
Abstract:
Regeneration of smooth muscle cells (SMCs) is vital in vascular remodeling. Sca1 + stem/progenitor cells (SPCs) can generate de novo smooth muscle cells after severe vascular injury during vessel repair and regeneration. However, the underlying mechanisms have not been conclusively determined. Here, we reported that lncRNA Metastasis-associated lung adenocarcinoma transcript 1 (Malat1) was down-regulated in various vascular diseases including arteriovenous fistula, artery injury and atherosclerosis. Using genetic lineage tracing mice and veingraft mice surgery model, we found that suppression of lncRNA Malat1 promoted Sca1 + cells to differentiate into SMCs in vivo, resulting in excess SMC accumulation in neointima and vessel stenosis. Genetic ablation of Sca1 + cells attenuated venous arterialization and impaired vascular structure normalization, and thus, resulting in less Malat1 down-regulation. Single cell sequencing further revealed a fibroblast-like phenotype of Sca1 + SPCs-derived SMCs. Protein array sequencing and in vitro assays revealed that SMC regeneration from Sca1 + SPCs was regulated by Malat1 through miR125a-5p/Stat3 signaling pathway. These findings delineate the critical role of Sca1 + SPCs in vascular remodeling and reveal that lncRNA Malat1 is a key regulator and might serve as a novel biomarker or potential therapeutic target for vascular diseases.
Type of Medium:
Online Resource
ISSN:
1420-682X
,
1420-9071
DOI:
10.1007/s00018-023-04762-3
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2023
detail.hit.zdb_id:
1458497-9
SSG:
12
