Acta NaturaeActa NaturaeActa Naturae2075-8251Acta Naturae Ltd1786310.32607/actanaturae.17863Research ArticlesЭкспериментальные статьиResearch ArticleELABELA-APJ Axis Enhances Mesenchymal Stem Cell Proliferation and Migration via the METTL3/PI3K/AKT PathwayXuD.
China
tongwang316@163.comFuJ.
China
tongwang316@163.comLiuX.
China
tongwang316@163.comHongY.
China
tongwang316@163.comChenX.
China
tongwang316@163.comLiS.
China
tongwang316@163.comHouJ.
China
tongwang316@163.comZhangK.
China
tongwang316@163.comZhouC.
China
tongwang316@163.comZengC.
China
tongwang316@163.comZhengG.
China
tongwang316@163.comWuH.
China
tongwang316@163.comWangT.
China
tongwang316@163.comDepartment of Emergency, the Eighth Affiliated Hospital of Sun Yat-sen UniversityDepartment of Emergency, the Sun Yat-sen Memorial Hospital of Sun Yat-sen UniversityDepartment of Emergency, the Sun Yat-sen Memorial Hospital of Sun Yat-sen UniversityDepartment of Emergency, the Eighth Affiliated Hospital of Sun Yat-sen University100520241611111182903202314022024Copyright ©; 2024, 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.Copyright ©; 2024, 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.2024Xu 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.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.https://creativecommons.org/licenses/by/4.0https://actanaturae.ru/2075-8251/article/view/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 in vitro 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 concentration-dependent 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 in vitro 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.

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