Caveolin-1 Plays an Important Role in the Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells into Cardiomyocytes

Abstract

Objectives: Accumulating evidence has demonstrated that bone marrow-derived mesenchymal stem cells (BMSCs) may transdifferentiate into cardiomyocytes, making BMSCs a promising source of cardiomyocytes for transplantation. However, little is known about the molecular mechanisms underlying myogenic conversion of BMSCs. Methods: This study was designed to investigate the functional role of caveolin-1 in the cardiomyocyte differentiation of BMSCs and to explore the potential underlying molecular mechanisms. Results: BMSC differentiation was induced by treatment with 10 μ<smlcap>M</smlcap> 5-azacytidine, and immunofluorescence assay showed that the expression of cardiomyocyte marker cardiac troponin T (cTnT) was significantly increased compared with a control group. Meanwhile, an increased caveolin-1 expression was found during the 5-azacytidine-induced BMSC differentiation. Additionally, the role of caveolin-1 in the differentiation process was then studied by using caveolin-1 siRNAs. We found that silencing caveolin-1 during induction remarkably enhanced the expression of cardiomyocyte marker genes, including cTnT, Nkx2.5 (cardiac-specific transcription factor), α-cardiac actin and α-myosin heavy chain (α-MHC). Moreover, we observed that downregulation of caveolin-1 was accompanied by inhibition of signal transducer and activator of transcription 3 (STAT3) phosphorylation. Conclusions: Taken together, these findings demonstrate that caveolin-1 plays an important role in the differentiation of BMSCs into cardiomyocytes in conjunction with the STAT3 pathway.