Long noncoding RNA Braveheart promotes cardiogenic differentiation of mesenchymal stem cells in vitro

Abstract

BackgroundMesenchymal stem cells (MSCs) have limited potential of cardiogenic differentiation. In this study, we investigated the influence of long noncoding RNA Braveheart (lncRNA-Bvht) on cardiogenic differentiation of MSCs in vitro.MethodsMSCs were obtained from C57BL/6 mice and cultured in vitro. Cells were divided into three groups: blank control, null vector control, and lncRNA-Bvht. All three groups experienced exposure to hypoxia (1% O2) and serum deprivation for 24 h, and 24 h of reoxygenation (20% O2). Cardiogenic differentiation was induced using 5-AZA for another 24 h. Normoxia (20% O2) was applied as a negative control during the whole process. Cardiogenic differentiation was assessed, and expressions of cardiac-specific transcription factors and epithelial-mesenchymal transition (EMT)-associated biomarkers were detected. Anti-mesoderm posterior1 (Mesp1) siRNA was transfected in order to block its expression, and relevant downstream molecules were examined.ResultsCompared with the blank control and null vector control groups, the lncRNA-Bvht group presented a higher percentage of differentiated cells of the cardiogenic phenotype in vitro both under the normal condition and after hypoxia/re-oxygenation. There was an increased level of cTnT and α-SA, and cardiac-specific transcription factors including Nkx2.5, Gata4, Gata6, and Isl-1 were significantly upregulated (P < 0.01). Expressions of EMT-associated genes including Snail, Twist and N-cadherin were much higher (P < 0.01). Mesp1 exhibited a distinct augmentation following lncRNA-Bvht transfection. Expressions of relevant cardiac-specific transcription factors and EMT-associated genes all presented a converse alteration in the condition of Mesp1 inhibition prior to lncRNA-Bvht transfection.ConclusionlncRNA-Bvht could efficiently promote MSCs transdifferentation into cells with the cardiogenic phenotype in vitro. It might function via enhancing the expressions of cardiac-specific transcription factors and EMT-associated genes. Mesp1 could be a pivotal intermediary in the procedure.

Mapping Trends and Identifying Hotspots in Research on Mesenchymal Stem Cells in Cardiovascular Disease

“…The Chinese Academy of Medical Sciences also explored the improvement of cardiac function by MSCs regulated by matrix-derived factor 1 (SDF1a) [48] and CXC chemokine receptor 4 (CXCR4) [49]. Sun Yat-sen University researched the effects of exons (Exo) [50], the TGF-β superfamily [51], the long noncoding RNA brave heart (lncRNA-Bvht) [52], apelin [53] and granulocyte colony stimulating factor (G-CSF) [54] on the proliferation, differentiation and vascularization of MSCs. The functions of the transcription factors islet-1 (ISL1) [55] and platelet brin (PRF) [56] in regulating the repair of myocardial infarction by MSCs have been explored.…”

Extracellular vesicle-mediated transport of non-coding RNAs between stem cells and cancer cells: implications in tumor progression and therapeutic resistance

“…Since ncRNAs are central to gene regulation and cellular fates, it can be speculated that most of the EV-mediated regulatory roles elicited in cells/organs are mediated through ncRNAs (18,37). Indeed, ncRNAs are expressed in tissue-specific manner, precisely regulated and actively involved in variety of developmental processes (43)(44)(45)(46)(47)(48)(49)(50), and the lineage specific commitments of stem cells and the maintenance of their characteristic features such as pluripotency, self-renewal, differentiation, and efficiency of cellular reprogramming are largely regulated by ncRNAs (51)(52)(53)(54)(55)(56)(57)(58)(59)(60). Thus, the ncRNAs may govern the equilibrium between pluripotency and differentiation in stem cells, as well as lineage specific fate decisions (61,62).…”

Concise Review: Challenges in Regenerating the Diabetic Heart: A Comprehensive Review

“…Recently, Hou et al showed the importance of Bvht in promoting the cardiogenic differentiation of MSC. Overexpression of Bvht in MSC isolated from mouse bone marrow showed a better cardiogenic differentiation and importantly inhibition of MesP1 significantly attenuated the transdifferentiation of MSC overexpressed with Bvht . Being a relatively newcomer to the family of lncRNA, the role of Bvht on CPCs and diabetes is still not known, although the evidence suggests Bvht as a strong candidate requiring further studies.…”