Xu D, Fu J, Liu X, Hong Y, Chen X, Li S, Hou J, Zhang K, Zhou C, Zeng C, Zheng G, Wu H, Wang T
Department of Emergency, the Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, 518003 China.
Department of Emergency, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510120 China.
Acta Naturae. 2024 Jan-Mar;16(1):111-118. doi: 10.32607/actanaturae.17863.
Mesenchymal stem cells (MSCs) possess a strong therapeutic potential in regenerative medicine. ELABELA (ELA) is a 32 amino acid peptide that binds to the apelin peptide jejunum receptor (APJ) to regulate cell proliferation and migration. The aim of this study was to investigate the function of ELA vis-a-vis the MSC proliferation and migration, and further explore the underlying mechanism. We demonstrated that the exogenous supplement of ELA boosts the proliferation and migration ability of MSCs, alongside improved cell viability. These capabilities were rendered moot upon APJ knockdown. In addition, ELA (5-20 μM) was shown to upregulate the expression of METTL3 in a concentrationdependent pattern, a capacity which was suppressed by APJ reduction, whereas the downregulation of METTL3 expression blocked the beneficial effects induced by ELA. ELA was also observed to upregulate the phosphorylation level of AKT. This ELA-induced activation of the PI3K/AKT pathway, however, is inhibited with knockdown of METTL3. Our data indicate that ELA could act as a promoter of MSC proliferation and migration through the APJ receptor, something which might be attributed to the activation of the METTL3/PI3K/AKT signaling pathway. Therefore, ELA is a candidate for optimizing MSC-based cell therapy, while METTL3 is a potential target for its promoting action on MSCs.
间充质干细胞（MSCs）在再生医学中具有强大的治疗潜力。ELABELA（ELA）是一种由32个氨基酸组成的肽，它与apelin肽空肠受体（APJ）结合，以调节细胞增殖和迁移。本研究的目的是研究ELA对MSCs增殖和迁移的作用，并进一步探索其潜在机制。我们证明，外源性补充ELA可提高MSCs的增殖和迁移能力，同时改善细胞活力。在敲低APJ后，这些能力失效。此外，ELA（5-20μM）呈浓度依赖性上调METTL3的表达，APJ减少可抑制这种能力，而METTL3表达的下调则阻断了ELA诱导的有益作用。还观察到ELA上调AKT的磷酸化水平。然而，敲低METTL3可抑制ELA诱导的PI3K/AKT途径的激活。我们的数据表明，ELA可能通过APJ受体作为MSCs增殖和迁移的促进剂，这可能归因于METTL3/PI3K/AKT信号通路的激活。因此，ELA是优化基于MSCs的细胞治疗的候选药物，而METTL3是其促进MSCs作用的潜在靶点。
