Alterations in Cardiomyocyte Differentiation-Related Proteins in Rat Mesenchymal Stem Cells Exposed to Hypoxia

Abstract

Background/Aims: It is known that mesenchymal stem cells (MSCs) can have variable responses to hypoxic conditions and that hypoxia may specifically stimulate differentiation into osteogenic, chondrogenic, or adipogenic cells. Based on our previous study, we hypothesized that hypoxia may also induce MSC differentiation into cardiomyocytes and/or cells with comparable phenotypes. Methods: The differences in the proteomes were specifically investigated in bone marrow-derived rat MSCs (BM-rMSCs) under normoxic and hypoxic conditions using 2-DE combined with a MALDI-TOF-MS analysis and western blot analysis. In addition, genetic and/or proteomic interactions were assessed using a String network analysis. Results: Among the 35 markedly changed spots from a total of 393 matched spots, 24 were highly up-regulated and 11 were significantly down-regulated in hypoxic rMSCs based on a proteomic analysis. Although hypoxia failed to induce the direct differentiation of rMSCs into cardiomyocytes, several cardiomyocyte differentiation-related genes and proteins were significantly increased by hypoxic stress. Conclusion: We found that BM-rMSCs alter their expression of several cardiomyocyte differentiation-related genes and proteins under hypoxic conditions, and we examined the interactions between these genes and/or proteins, providing new insights for the applicability of MSCs preconditioned by hypoxic stimulation for use in cardiac diseases.

Keywords

• Bone marrow-derived rat mesenchymal stem cells
• Hypoxia
• Cardiomyocyte differentiation
• Two-dimensional electrophoresis
• Network analysis