Celastrol mitigates high glucose-induced inflammation and apoptosis in rat H9c2 cardiomyocytes via miR-345-5p/growth arrest-specific 6
| Autor: | Yizhan Pan, Laixing Yan, Liping Ma, Yanjing Cao, Ketao Li, Lin Zhang, Jianhua Zhu |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Inflammation Apoptosis Flow cytometry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Drug Discovery Genetics medicine Animals Humans Myocytes Cardiac Molecular Biology Cell damage Genetics (clinical) medicine.diagnostic_test GAS6 Transfection medicine.disease Cell biology Rats MicroRNAs 030104 developmental biology Glucose chemistry Proto-Oncogene Proteins c-bcl-2 Celastrol 030220 oncology & carcinogenesis Molecular Medicine Intercellular Signaling Peptides and Proteins medicine.symptom Signal transduction Pentacyclic Triterpenes Signal Transduction |
| Zdroj: | The journal of gene medicineREFERENCES. 22(9) |
| ISSN: | 1521-2254 |
| Popis: | Background Celastrol (Cel) has been corroborated as an anti-inflammatory and anti-apoptotic agent in multiple cell damage models. However, the protective effect of Cel in high glucose (HG)-induced cardiomyocyte injury is still unclear. The present study aimed to determine whether Cel can mitigate HG-stimulated cardiomyocyte injury via regulating the miR-345-5p/growth arrest-specific 6 (Gas6) signaling pathway. Methods Cardiomyocytes were exposed to normal glucose (NG; 5 mmol/l) or HG (30 mmol/l) and then administered with Cel. Cell counting kit-8 and flow cytometry assays were used to detect cell proliferative activity and apoptosis. mRNA and protein expression were analyzed using a quantitative reverse transcriptase-polymerase chain reaction and western blotting, respectively. A bioinformatics algorithm and a luciferase reporter gene assay were used to determine whether Gas6 is a direct target of miR-345-5p. Results The present study confirmed the inhibitory effects of Cel in HG-induced inflammation in cardiomyocytes. Moreover, Cel exhibited the ability to antagonize HG-induced cardiomyocyte apoptosis and suppress the elevated Bax/Bcl-2 ratio elicited by HG stimulation. Intriguingly, Cel treatment revoked the HG-triggered repression of Gas6 protein expression, and Gas6 loss-of-function accelerated HG-induced cardiomyocyte apoptosis. HG-triggered up-regulation of miR-345-5p expression was depressed following Cel treatment. Importantly, we validated that Gas6 is a direct target of miR-345-5p. Transfection with miR-345-5p inhibitors restrained HG-induced release of pro-inflammatory cytokines and cell apoptosis. Conclusions The findings of the present study demonstrate that Cel administration antagonized HG-induced cardiomyocyte apoptosis and inflammation through up-regulating Gas6 expression by restraining miR-345-5p. |
| Databáze: | OpenAIRE |
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