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Inhibition of NF-κB and Wnt/β-catenin/GSK3β Signaling Pathways Ameliorates Cardiomyocyte Hypertrophy and Fibrosis in Streptozotocin (STZ)-induced Type 1 Diabetic Rats

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Summary

Type 1 diabetes mellitus (T1DM) is associated with an increased risk of diabetic cardiomyopathy (DCM). Nuclear factor kappa B (NF-κB) and Wnt/β-catenin/GSK3β have been demonstrated to play pathogenic roles in diabetes. In this study, we evaluated the roles of these two pathways in T1DM-induced cardiomyopathy in rats. Streptozotocin (STZ)-induced type 1 diabetic rats were treated with pyrrolidine dithiocarbamate (PDTC) or meisoindigo (Me) to inhibit NF-κB and Wnt/β-catenm/GSK3β respectively for 4 or 8 weeks. As compared with untreated diabetic rats, treatment with either PDTC or Me partly attenuated the myocardial hypertrophy and interstitial fibrosis, improved cardiac function, and exhibited reduction in inflammatory reaction. In addition, we found that inhibiting NF-κB and Wnt/β-catenin/GSK3β pathways could regulate glucose and lipid metabolism. The effects were associated with the decrease of NF-κB activity and the downregulation of some proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-2. Our data suggested that the activities of NF-κB and Wnt/β-catenin/GSK3β pathways were both increased and inhibiting NF-κB and Wnt/β-catenin/GSK3β signaling pathways might improve myocardial injury in T1DM rats.

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Author notes

  1. The two authors contributed equally to this work and they are co-first authors of this article.

Authors and Affiliations

  1. School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, 250200, China

    Jing-jing Liu

  2. Institute of Materia Medica, Shandong Academy of Medical Sciences, Jinan, 250062, China

    Jing-jing Liu, Lu-mei Shentu, Ning Ma, Yan Wang, Jun Li & Yan-ling Mu

  3. Key Laboratory for Biotech-Drugs Ministry of Health, Jinan, 250062, China

    Lu-mei Shentu, Ning Ma, Yan Wang, Jun Li & Yan-ling Mu

  4. Key Laboratory for Rare & Uncommon Diseases of Shandong Province, Jinan, 250062, China

    Lu-mei Shentu, Ning Ma, Yan Wang, Jun Li & Yan-ling Mu

  5. Shandong Electric Power Central Hospital, Jinan, 250001, China

    Li-ying Wang

  6. Laboratory, Generic Manufacture Technology of Chinese Traditional Medicine, Jinan, 250001, China

    Gui-min Zhang & Ying Sun

  7. Center for New Drug Pharmacological Research of Lunan Pharmaceutical Group, Jinan, 250001, China

    Gui-min Zhang & Ying Sun

Authors
  1. Jing-jing Liu
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  2. Lu-mei Shentu
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  3. Ning Ma
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  4. Li-ying Wang
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  5. Gui-min Zhang
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  6. Ying Sun
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  7. Yan Wang
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  8. Jun Li
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  9. Yan-ling Mu
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Corresponding author

Correspondence to Yan-ling Mu.

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Conflict of Interest Statement

No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication.

This project was supported by the Research Award Fund for Outstanding Young Scientists Plan in Shandong Province of China (No. BS2013SW008), and the Innovation Project of Shandong Academy of Medical Sciences.

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Liu, Jj., Shentu, Lm., Ma, N. et al. Inhibition of NF-κB and Wnt/β-catenin/GSK3β Signaling Pathways Ameliorates Cardiomyocyte Hypertrophy and Fibrosis in Streptozotocin (STZ)-induced Type 1 Diabetic Rats. CURR MED SCI 40, 35–47 (2020). https://doi.org/10.1007/s11596-020-2144-x

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  • DOI: https://doi.org/10.1007/s11596-020-2144-x

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