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Article

miR‑155 modulates high glucose‑induced cardiac fibrosis via the Nrf2/HO‑1 signaling pathway

  • Authors:
    • Yu Li
    • Jing‑Zhu Duan
    • Qian He
    • Chong‑Quan Wang
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China, Department of Respiratory Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China
  • Pages: 4003-4016
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    Published online on: September 7, 2020
       https://doi.org/10.3892/mmr.2020.11495
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Abstract

Cardiac fibrosis is a major pathological manifestation of diabetic cardiomyopathy, which is a leading cause of mortality in patients with diabetes. MicroRNA (miR)‑155 is upregulated in cardiomyocytes in cardiac fibrosis, and the aim of the present study was to investigate if the inhibition of miR‑155 was able to ameliorate cardiac fibrosis by targeting the nuclear factor erythroid‑2‑related factor 2 (Nrf2)/heme oxygenase‑1 (HO‑1) signaling pathway. H9C2 rat cardiomyocytes were cultured with high glucose (HG; 30 mM) to establish an in vitro cardiac fibrosis model that mimicked diabetic conditions; a miR‑155 inhibitor and a miR‑155 mimic were transfected into H9C2 cells. Following HG treatment, H9C2 cells exhibited increased expression levels of miR‑155 and the fibrosis markers collagen I and α‑smooth muscle actin (α‑SMA). In addition, the expression levels of endonuclear Nrf2 and HO‑1 were decreased, but the expression level of cytoplasmic Nrf2 was increased. Moreover, oxidative stress, mitochondrial damage and cell apoptosis were significantly increased, as indicated by elevated reactive oxygen species, malonaldehyde and monomeric JC‑1 expression levels. In addition, superoxide dismutase expression was attenuated and there was an increased expression level of released cytochrome‑c following HG treatment. Furthermore, it was demonstrated that expression levels of Bcl‑2 and uncleaved Poly (ADP‑ribose) polymerase were downregulated, whereas Bax, cleaved caspase‑3 and caspase‑9 were upregulated after HG treatment. However, the miR‑155 inhibitor significantly restored Nrf2 and HO‑1 expression levels, and reduced oxidative stress levels, the extent of mitochondrial damage and the number of cells undergoing apoptosis. Additionally, the miR‑155 inhibitor significantly reversed the expression levels of collagen I and α‑SMA, thus ameliorating fibrosis. Furthermore, the knockdown of Nrf2 reversed the above effects induced by the miR‑155 inhibitor. In conclusion, the miR‑155 inhibitor may ameliorate diabetic cardiac fibrosis by reducing the accumulation of oxidative stress‑related molecules, and preventing mitochondrial damage and cardiomyocyte apoptosis by enhancing the Nrf2/HO‑1 signaling pathway. This mechanism may facilitate the development of novel targets to prevent cardiac fibrosis in patients with diabetes.
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Copy and paste a formatted citation
Spandidos Publications style
Li Y, Duan JZ, He Q and Wang CQ: miR‑155 modulates high glucose‑induced cardiac fibrosis via the Nrf2/HO‑1 signaling pathway. Mol Med Rep 22: 4003-4016, 2020.
APA
Li, Y., Duan, J., He, Q., & Wang, C. (2020). miR‑155 modulates high glucose‑induced cardiac fibrosis via the Nrf2/HO‑1 signaling pathway. Molecular Medicine Reports, 22, 4003-4016. https://doi.org/10.3892/mmr.2020.11495
MLA
Li, Y., Duan, J., He, Q., Wang, C."miR‑155 modulates high glucose‑induced cardiac fibrosis via the Nrf2/HO‑1 signaling pathway". Molecular Medicine Reports 22.5 (2020): 4003-4016.
Chicago
Li, Y., Duan, J., He, Q., Wang, C."miR‑155 modulates high glucose‑induced cardiac fibrosis via the Nrf2/HO‑1 signaling pathway". Molecular Medicine Reports 22, no. 5 (2020): 4003-4016. https://doi.org/10.3892/mmr.2020.11495
Copy and paste a formatted citation
x
Spandidos Publications style
Li Y, Duan JZ, He Q and Wang CQ: miR‑155 modulates high glucose‑induced cardiac fibrosis via the Nrf2/HO‑1 signaling pathway. Mol Med Rep 22: 4003-4016, 2020.
APA
Li, Y., Duan, J., He, Q., & Wang, C. (2020). miR‑155 modulates high glucose‑induced cardiac fibrosis via the Nrf2/HO‑1 signaling pathway. Molecular Medicine Reports, 22, 4003-4016. https://doi.org/10.3892/mmr.2020.11495
MLA
Li, Y., Duan, J., He, Q., Wang, C."miR‑155 modulates high glucose‑induced cardiac fibrosis via the Nrf2/HO‑1 signaling pathway". Molecular Medicine Reports 22.5 (2020): 4003-4016.
Chicago
Li, Y., Duan, J., He, Q., Wang, C."miR‑155 modulates high glucose‑induced cardiac fibrosis via the Nrf2/HO‑1 signaling pathway". Molecular Medicine Reports 22, no. 5 (2020): 4003-4016. https://doi.org/10.3892/mmr.2020.11495
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