Expression profiles of long noncoding RNAs in cardiac stem cells under hyperglycemic conditions

Background/Aims: Hyperglycemia is an important risk factor for the most severe cardiovascular diseases in patients with diabetes. It has been demonstrated that cardiac stem cells (CSCs) play a pivotal role in the maintenance of cardiac homeostasis and regeneration. However, the mechanism underlying the influence of diabetes on CSCs remains unclear. This study demonstrated that hyperglycemia might promote adipogenesis in CSCs, which induces a decline in myocardial regeneration capability in diabetes. Methods: CSCs were isolated and cultured in high-glucose medium. The levels of β-catenin and TCF-4 in CSCs were determined by immunofluorescence staining and western blot analysis. Adipogenic transcriptional factors and CSCs markers were also examined by flow cytometry and western blot analysis after adipogenesis induction. In addition, Oil Red O staining was performed to investigate lipid droplet formation during adipogenesis induction with or without LiCl, a potent activator of TCF/β-catenin-dependent transcription. Results: High-glucose conditions inhibited nuclear translocation of β-catenin/TCF-4 and promoted adipogenesis in CSCs. After adipogenesis induction, expression of adipogenic transcriptional factors (PPARγ, ADD1, and C/EBPα) were increased (P < 0.01) and that of CSCs markers (c-Kit, Sca-1, MDR-1, and isl-1) were decreased (P< 0.01) in CSCs in the high-glucose group. Furthermore, lipid droplet formation was increased in CSCs cultured with high glucose, while LiCl attenuated lipid droplet formation in these CSCs (P < 0.01). Conclusion: These results demonstrated that hyperglycemia inhibited the β-catenin/TCF-4 pathway and promoted CSCs adipogenesis. Our findings suggest a new opportunity for future interventional strategie for abnormal myocardial regeneration and epicardial fat in patients with diabetes.

show abstract

“…1B). Thus, we confirmed in this study that these cells were CSCs, as in our previous studies [20,21].…”

Section: Characteristics Of Cscssupporting

confidence: 92%

“…CSCs were isolated from the hearts of 1-to 3-day-old neonatal Sprague-Dawley rats as we described previously [20,21]. CSCs at cell passage 1 were evaluated by flow cytometry using the Becton-Dickinson FACSCaliber (BD Bioscience, San Jose, CA) with 10, 000 events collected to confirm the cells were CSCs.…”

Section: Isolation Of Cscs and High-glucose Treatmentmentioning

confidence: 99%

Hyperglycemia Altered the Fate of Cardiac Stem Cells to Adipogenesis through Inhibiting the β-Catenin/TCF-4 Pathway

Zhang

Meng

et al. 2018

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

show abstract

“…Most research efforts focus on differential LncRNA expression during the disease process [22, 23]. However, the real mechanism or function of LncRNAs has not been completely clarified.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of LncRNA-HRIM Increases Cell Viability by Regulating Autophagy Levels During Hypoxia/Reoxygenation in Myocytes

Huang¹,

Ye²,

Wang³

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Backgrund/Aims: Ischemia reperfusion (I/R) promotes the severity of cardiomyocyte injury. Long noncoding RNAs (LncRNAs) are key regulators in cardiovascular diseases. However, the association between LncRNAs and myocardial I/R injury has not been thoroughly characterized to date. We attempted to clarify the potential biological role of a LncRNA (E230034O05Rik), which we named hypoxia/reoxygenation (H/R) injury-related factor in myocytes (HRIM), by investigating the differential expression of LncRNAs between groups of myocytes exposed to either a normal level of oxygen or to H/R. Methods: Microarray analysis was used to determine analyze the global differential expression of LncRNAs in H9c2 myocytes exposed either to a normal level of oxygen or to H/R. Target LncRNA levels were further verified in vitro and ex vivo by real-time polymerase chain reaction (qPCR). Cell viability was analyzed using the Cell Counting Kit-8 assay. Autophagy levels were confirmed by Western blotting, transmission electron microscopy, and autophagic double-labeled (mRFP-GFP-LC3) adenovirus analyses. Results: Gene expression profiling revealed that 797 LncRNAs and 1898 mRNAs were differentially expressed in the H/R group compared with the normal oxygen group. Among these LncRNAs and mRNAs, 6 upregulated LncRNAs and 2 downregulated LncRNAs in the H/R group were selected and further validated by qPCR in vitro and ex vivo. Additionally, LncRNA-HRIM was inhibited by specific siRNAs in H9c2 myocytes exposed to H/R. The inhibition of LncRNA-HRIM by siRNA prevented cell death by suppressing excessive autophagic activity in myocytes, This finding suggests a detrimental role of LncRNA-HRIM in the regulation of I/R injury. Conclusions: LncRNAs are involved in H/R injury of H9c2 myocytes. Inhibition of LncRNA-HRIM increased cell viability by reducing autophagy in myocytes during H/R.

show abstract

Transforming growth factor beta (TGF-β) mediates cardiac fibrosis and induces diabetic cardiomyopathy

Yue

Meng

et al. 2017

Diabetes Research and Clinical Practice

180

126

View full text Add to dashboard Cite

Expression profiles of long noncoding RNAs in cardiac stem cells under hyperglycemic conditions

Cited by 4 publications

References 27 publications

Hyperglycemia Altered the Fate of Cardiac Stem Cells to Adipogenesis through Inhibiting the β-Catenin/TCF-4 Pathway

Hyperglycemia Altered the Fate of Cardiac Stem Cells to Adipogenesis through Inhibiting the β-Catenin/TCF-4 Pathway

Inhibition of LncRNA-HRIM Increases Cell Viability by Regulating Autophagy Levels During Hypoxia/Reoxygenation in Myocytes

Transforming growth factor beta (TGF-β) mediates cardiac fibrosis and induces diabetic cardiomyopathy

Contact Info

Product

Resources

About