Zheng Yue, Liu Hua, Kong Ye
Department of Cardiothoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, China.
Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, China.
FEBS Lett. 2017 Aug;591(15):2290-2298. doi: 10.1002/1873-3468.12720. Epub 2017 Jul 19.
Lineage-negative bone marrow cells (lin-BMCs) have reparative potential for overcoming endothelial dysfunction and reducing cardiovascular risk. Here, we found that miR-188 is upregulated and mitogen-activated protein kinase kinase kinase 3 (MAP3K3) is downregulated in aged lin-BMCs, whereas their expression is reversed in young lin-BMCs. We identified and confirmed MAP3K3 as a direct target of miR-188. MiR-188 overexpression or MAP3K3 silencing in young lin-BMCs increases p16 and p21 expression, enhances cell senescence, and decreases the ability for cell proliferation, migration, and tube formation. Conversely, miR-188 suppression in aged lin-BMCs yields the opposite results. We further found that MAP3K3 is involved in miR-188-induced promotion of lin-BMC senescence. All data reveal that miR-188 induces lin-BMC senescence by targeting MAP3K3 expression, thus, providing new theoretical basis for the prevention and treatment of cardiovascular diseases.
谱系阴性骨髓细胞（lin-BMCs）具有修复潜力，可克服内皮功能障碍并降低心血管风险。在此，我们发现老年lin-BMCs中miR-188上调而丝裂原活化蛋白激酶激酶激酶3（MAP3K3）下调，而在年轻lin-BMCs中它们的表达则相反。我们鉴定并证实MAP3K3是miR-188的直接靶标。年轻lin-BMCs中miR-188过表达或MAP3K3沉默会增加p16和p21表达，增强细胞衰老，并降低细胞增殖、迁移和管形成能力。相反，老年lin-BMCs中miR-188抑制产生相反的结果。我们进一步发现MAP3K3参与了miR-188诱导的lin-BMC衰老促进过程。所有数据表明，miR-188通过靶向MAP3K3表达诱导lin-BMC衰老，从而为心血管疾病的预防和治疗提供了新的理论依据。
