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Article

Spleen tyrosine kinase‑induced JNK‑dependent NLRP3 activation is involved in diabetic cardiomyopathy

  • Authors:
    • Shengyu Li
    • Ruiqing Liu
    • Meiting Xue
    • Yingchun Qiao
    • Yufeng Chen
    • Guangfeng Long
    • Xixi Tian
    • Yahui Hu
    • Pengfei Zhou
    • Xiaohui Dong
    • Zhi Qi
    • Yujie Cui
    • Yanna Shen
  • View Affiliations / Copyright

    Affiliations: School of Medical Laboratory, Tianjin Medical University, Tianjin 300203, P.R. China, Department of Histology and Embryology, School of Medicine, Nankai University, Tianjin 300071, P.R. China
  • Pages: 2481-2490
    |
    Published online on: March 27, 2019
       https://doi.org/10.3892/ijmm.2019.4148
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Abstract

Diabetic cardiomyopathy (DCM) is a leading contributor to the increased morbidity and mortality rates associated with diabetes. Persistent inflammation has previously been reported to be involved in the pathogenesis of DCM. However, the exact underlying molecular mechanisms remain to be fully elucidated. In the present study, the role of spleen tyrosine kinase (Syk) and c‑Jun N‑terminal kinase (JNK) in NLR family pyrin domain‑containing 3 (NLRP3 inflammasome) activation in DCM were investigated in vivo and in vitro. Streptozotocin (65 mg/kg) was injected intraperitoneally into Sprague‑Dawley rats to induce a rat model of diabetes. Neonatal rat cardiomyocytes and H9c2 cells were cultured to detect the expression of JNK, NLRP3 and its associated downstream molecules, following treatment with Syk/JNK inhibitor or Syk/JNK‑small interfering (si)RNA in high glucose (HG) conditions. It was revealed that the protein and mRNA expression levels of phospho (p)‑Syk, p‑JNK, NLRP3 and its associated downstream molecules, including interleukin (IL)‑1β, were upregulated in vivo and in vitro. The JNK inhibitor significantly decreased the expression of NLRP3 and its downstream molecules in neonatal rat cardiomyocytes and H9c2 cells treated with HG. Furthermore, Syk‑siRNA and the Syk inhibitor markedly inhibited the HG‑induced activation of JNK, followed by the downregulation of NLRP3 and its downstream molecules at the mRNA and protein levels in cells. Therefore, it was demonstrated that the HG‑induced activation of NLRP3 was mediated by the activation of Syk/JNK, which subsequently increased the protein expression levels of mature IL‑1β, suggesting that the Syk/JNK/NLRP3 signaling pathway serves a critical role in the pathogenesis of DCM.
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Copy and paste a formatted citation
Spandidos Publications style
Li S, Liu R, Xue M, Qiao Y, Chen Y, Long G, Tian X, Hu Y, Zhou P, Dong X, Dong X, et al: Spleen tyrosine kinase‑induced JNK‑dependent NLRP3 activation is involved in diabetic cardiomyopathy. Int J Mol Med 43: 2481-2490, 2019.
APA
Li, S., Liu, R., Xue, M., Qiao, Y., Chen, Y., Long, G. ... Shen, Y. (2019). Spleen tyrosine kinase‑induced JNK‑dependent NLRP3 activation is involved in diabetic cardiomyopathy. International Journal of Molecular Medicine, 43, 2481-2490. https://doi.org/10.3892/ijmm.2019.4148
MLA
Li, S., Liu, R., Xue, M., Qiao, Y., Chen, Y., Long, G., Tian, X., Hu, Y., Zhou, P., Dong, X., Qi, Z., Cui, Y., Shen, Y."Spleen tyrosine kinase‑induced JNK‑dependent NLRP3 activation is involved in diabetic cardiomyopathy". International Journal of Molecular Medicine 43.6 (2019): 2481-2490.
Chicago
Li, S., Liu, R., Xue, M., Qiao, Y., Chen, Y., Long, G., Tian, X., Hu, Y., Zhou, P., Dong, X., Qi, Z., Cui, Y., Shen, Y."Spleen tyrosine kinase‑induced JNK‑dependent NLRP3 activation is involved in diabetic cardiomyopathy". International Journal of Molecular Medicine 43, no. 6 (2019): 2481-2490. https://doi.org/10.3892/ijmm.2019.4148
Copy and paste a formatted citation
x
Spandidos Publications style
Li S, Liu R, Xue M, Qiao Y, Chen Y, Long G, Tian X, Hu Y, Zhou P, Dong X, Dong X, et al: Spleen tyrosine kinase‑induced JNK‑dependent NLRP3 activation is involved in diabetic cardiomyopathy. Int J Mol Med 43: 2481-2490, 2019.
APA
Li, S., Liu, R., Xue, M., Qiao, Y., Chen, Y., Long, G. ... Shen, Y. (2019). Spleen tyrosine kinase‑induced JNK‑dependent NLRP3 activation is involved in diabetic cardiomyopathy. International Journal of Molecular Medicine, 43, 2481-2490. https://doi.org/10.3892/ijmm.2019.4148
MLA
Li, S., Liu, R., Xue, M., Qiao, Y., Chen, Y., Long, G., Tian, X., Hu, Y., Zhou, P., Dong, X., Qi, Z., Cui, Y., Shen, Y."Spleen tyrosine kinase‑induced JNK‑dependent NLRP3 activation is involved in diabetic cardiomyopathy". International Journal of Molecular Medicine 43.6 (2019): 2481-2490.
Chicago
Li, S., Liu, R., Xue, M., Qiao, Y., Chen, Y., Long, G., Tian, X., Hu, Y., Zhou, P., Dong, X., Qi, Z., Cui, Y., Shen, Y."Spleen tyrosine kinase‑induced JNK‑dependent NLRP3 activation is involved in diabetic cardiomyopathy". International Journal of Molecular Medicine 43, no. 6 (2019): 2481-2490. https://doi.org/10.3892/ijmm.2019.4148
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