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Silencing lncRNA GAS5 alleviates apoptosis and fibrosis in diabetic cardiomyopathy by targeting miR-26a/b-5p

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Abstract

Background

LncRNA GAS5 is associated with high glucose-induced cardiomyocyte injury, but its role in diabetic cardiomyopathy (DCM) remains unclear.

Methods

Mice were administered with streptozotocin to construct the diabetic model (DM). Primary mouse cardiomyocytes were isolated and treated with 30 mmol/L high glucose to mimic the diabetic condition in vitro. GAS5 expression was detected by quantitative reverse transcription polymerase chain reaction. The relationship between GAS5 and miR-26a/b-5p was determined by bioinformatic prediction, luciferase reporter assay and RNA immunoprecipitation assay. The cardiac function of diabetic mice was evaluated by two-dimensional echocardiography.

Results

GAS5 was significantly upregulated in diabetic cardiomyopathy both in vitro and in vivo. GAS5 knockdown and miR-26a/b-5p overexpression not only effectively attenuated myocardial fibrosis of diabetic mice in vivo but also inhibited high glucose-induced cardiomyocyte injury in vitro. miR-26a/b-5p was identified as a target of GAS5. GAS5 knockdown efficiently attenuated myocardial fibrosis and high glucose-induced cardiomyocyte injury through negatively regulating miR-26a/b-p.

Conclusion

Our study showed that GAS5 promotes DCM progression by regulating miR-26a/b-5p, suggesting that GAS5 might be a potential therapeutic target for DCM.

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Authors and Affiliations

  1. Department of Cardiac Function, The First Hospital of Qiqihar & Affiliated Qiqihar Hospital, Southern Medical University, Qiqihar, 161005, Heilongjiang, People’s Republic of China

    Chunping Zhu

  2. The Second Department of Endocrinology, The First Hospital of Qiqihar & Affiliated Qiqihar Hospital, Southern Medical University, No. 30 Park Road, Longsha, Qiqihar, 161005, Heilongjiang, People’s Republic of China

    Haijun Zhang & Zhe Sun

  3. Department of Traditional Chinese Medicine Geriatrics, The First Hospital of Qiqihar & Affiliated Qiqihar Hospital, Southern Medical University, Qiqihar, 161005, Heilongjiang, People’s Republic of China

    Dongmei Wei

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  1. Chunping Zhu
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  4. Zhe Sun
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Contributions

CZ, HZ: study concepts, literature research, clinical studies, data analysis, experimental studies, manuscript writing and review; DW: study design, literature research, experimental studies and manuscript editing; ZS: definition of intellectual content, clinical studies, data acquisition and statistical analysis.

Corresponding author

Correspondence to Haijun Zhang.

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All other authors have no conflicts of interest.

Ethical approval

This study was approved by the Animal Ethics Committee of the First Hospital of Qiqihar & Affiliated Qiqihar Hospital, Southern Medical University and conducted following the Announcement of Helsinki and laboratory guidelines of research in China.

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Zhu, C., Zhang, H., Wei, D. et al. Silencing lncRNA GAS5 alleviates apoptosis and fibrosis in diabetic cardiomyopathy by targeting miR-26a/b-5p. Acta Diabetol 58, 1491–1501 (2021). https://doi.org/10.1007/s00592-021-01745-3

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