Fate mapping RNA-sequencing reveal Malat1 regulates Sca1+ progenitor cells to vascular smooth muscle cells transition in vascular remodeling

التفاصيل البيبلوغرافية
العنوان: Fate mapping RNA-sequencing reveal Malat1 regulates Sca1+ progenitor cells to vascular smooth muscle cells transition in vascular remodeling
المؤلفون: Lingxia Lyu, Zhoubin Li, Zuoshi Wen, Yongchun He, Xuliang Wang, Liujun Jiang, Xuhao Zhou, Chengchen Huang, Yutao Wu, Ting Chen, Xiaogang Guo
المصدر: Cellular and Molecular Life Sciences. 80
بيانات النشر: Springer Science and Business Media LLC, 2023.
سنة النشر: 2023
مصطلحات موضوعية: Pharmacology, Cellular and Molecular Neuroscience, Molecular Medicine, Cell Biology, Molecular Biology
الوصف: 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.
تدمد: 1420-9071
1420-682X
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::4b294e35c95b1f87f3819827458dc004
https://doi.org/10.1007/s00018-023-04762-3
حقوق: OPEN
رقم الأكسشن: edsair.doi...........4b294e35c95b1f87f3819827458dc004
قاعدة البيانات: OpenAIRE