Cardiac progenitor cell‑derived exosomes promote H9C2 cell growth via Akt/mTOR activation

• Published in: International journal of molecular medicine 2018-09, Vol.42 (3), p.1517-1525
• Main Authors: Li, Shentang, Jiang, Jie, Yang, Zuocheng, Li, Zhuoying, Ma, Xing, Li, Xin
• Format: Article
• Language: English
• Subjects: Apoptosis; Autophagy; Cardiovascular diseases; Care and treatment; Cell cycle; Cell growth; Cellular signal transduction; Communication; Development and progression; Growth factors; Health aspects; Heart; Ischemia; Kinases; Labeling; Metabolism; Organelles; Protein synthesis; Proteins; Regulation; Rodents; Stem cells; Studies
• ISSN: 1107-3756; 1791-244X
• DOI: 10.3892/ijmm.2018.3699

Exosomes are cell-derived vesicles released from a variety of mammalian cells that are involved in cell-to-cell signalling. It has been reported that cardiac progenitor cells (CPCs) derived from an adult heart are one of the most promising stem cell types for cardioprotection and repair. The mammalian target of rapamycin (mTOR) signalling pathway is a pivotal regulator in CPCs, therefore, CPC-derived exosomes were used in the present study to investigate whether it can promote H9C2 cell growth through the protein kinase B (PKB, or Akt)/mTOR signalling pathway. The CPCs were isolated from Sprague-Dawley hearts. Following treatment with a specific medium, the exosomes were purified and identified by electron micrograph and western blot assays, using CD63 and CD81 as markers. The methyl-thiazolyl-tetrazolium and 5-ethynyl-2'-deoxyuridine methods were used to detect H9C2 cell growth. The expression of Akt and mTOR were detected by western blot analysis following treatment with 200 or 400 [micro]g/ml of exosomes for 24 or 48 h, respectively. It was found that, compared with higher concentrations of exosomes, prolonging the duration of exposure promoted cell growth. Accordingly, CPC-derived exosomes stimulated the expression of Akt to a marked degree; groups treated with exosomes for 48 h showed higher expression of Akt than those treated for 24 h at the same concentration. mTOR was also stimulated by CPC-derived exosomes. The activation of mTOR increased in accordance with the treatment time at an exosome concentration of 200 [micro]g/ml and decreased with treatment time at an exosome concentration of 400 [micro]g/ml. In conclusion, the present study demonstrated that CPC-derived exosomes promoted H9C2 cell growth via the activation of Akt/mTOR in a time-dependent manner at a relatively low exosome concentration, which may provide a novel therapy for cardiovascular disease.