Open Access

Spleen tyrosine kinase promotes NLR family pyrin domain containing 3 inflammasome‑mediated IL‑1β secretion via c‑Jun N‑terminal kinase activation and cell apoptosis during diabetic nephropathy

  • Authors:
    • Yingchun Qiao
    • Xixi Tian
    • Li Men
    • Shengyu Li
    • Yufeng Chen
    • Meiting Xue
    • Yahui Hu
    • Pengfei Zhou
    • Guangfeng Long
    • Yue Shi
    • Ruiqing Liu
    • Yunde Liu
    • Zhi Qi
    • Yujie Cui
    • Yanna Shen
  • View Affiliations

  • Published online on: June 14, 2018     https://doi.org/10.3892/mmr.2018.9164
  • Pages: 1995-2008
  • Copyright: © Qiao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Diabetic nephropathy (DN) is a serious complication of diabetes and can cause an increased mortality risk. It was previously reported that NLR family pyrin domain containing 3 (NLRP3) inflammasome is involved in the pathogenesis of diabetes. However, the underlying mechanism is not clearly understood. In the present study, the effects of spleen tyrosine kinase (Syk) and c‑Jun N‑terminal kinase (JNK) on the NLRP3 inflammasome were examined in vivo and in vitro. Sprague‑Dawley rats were injected intraperitoneally with streptozotocin (65 mg/kg) to induce diabetes. HK2 cells and rat glomerular mesangial cells (RGMCs) were examined to detect the expression of JNK and NLRP3 inflammasome‑associated proteins following treatment with a Syk inhibitor or Syk‑small interfering (si)RNA in a high glucose condition. In the present study, it was revealed that the protein and mRNA expression levels of NLRP3 inflammasome‑associated molecules and the downstream mature interleukin (IL)‑1β were upregulated in vivo and in vitro. The Syk inhibitor and Syk‑siRNA suppressed high glucose‑induced JNK activation, and subsequently downregulated the activation of the NLRP3 inflammasome and mature IL‑1β in HK2 cells and RGMCs. Furthermore, high glucose‑induced apoptosis of HK2 cells was reduced by the Syk inhibitor BAY61‑3606. Therefore, the present results determined that high glucose‑induced activation of the NLRP3 inflammasome is mediated by Syk/JNK activation, which subsequently increased the protein expression level of IL‑1β and mature IL‑1β. The present study identified that the Syk/JNK/NLRP3 signaling pathway may serve a vital role in the pathogenesis of DN.
View Figures
View References

Related Articles

Journal Cover

August-2018
Volume 18 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Qiao Y, Tian X, Men L, Li S, Chen Y, Xue M, Hu Y, Zhou P, Long G, Shi Y, Shi Y, et al: Spleen tyrosine kinase promotes NLR family pyrin domain containing 3 inflammasome‑mediated IL‑1β secretion via c‑Jun N‑terminal kinase activation and cell apoptosis during diabetic nephropathy. Mol Med Rep 18: 1995-2008, 2018.
APA
Qiao, Y., Tian, X., Men, L., Li, S., Chen, Y., Xue, M. ... Shen, Y. (2018). Spleen tyrosine kinase promotes NLR family pyrin domain containing 3 inflammasome‑mediated IL‑1β secretion via c‑Jun N‑terminal kinase activation and cell apoptosis during diabetic nephropathy. Molecular Medicine Reports, 18, 1995-2008. https://doi.org/10.3892/mmr.2018.9164
MLA
Qiao, Y., Tian, X., Men, L., Li, S., Chen, Y., Xue, M., Hu, Y., Zhou, P., Long, G., Shi, Y., Liu, R., Liu, Y., Qi, Z., Cui, Y., Shen, Y."Spleen tyrosine kinase promotes NLR family pyrin domain containing 3 inflammasome‑mediated IL‑1β secretion via c‑Jun N‑terminal kinase activation and cell apoptosis during diabetic nephropathy". Molecular Medicine Reports 18.2 (2018): 1995-2008.
Chicago
Qiao, Y., Tian, X., Men, L., Li, S., Chen, Y., Xue, M., Hu, Y., Zhou, P., Long, G., Shi, Y., Liu, R., Liu, Y., Qi, Z., Cui, Y., Shen, Y."Spleen tyrosine kinase promotes NLR family pyrin domain containing 3 inflammasome‑mediated IL‑1β secretion via c‑Jun N‑terminal kinase activation and cell apoptosis during diabetic nephropathy". Molecular Medicine Reports 18, no. 2 (2018): 1995-2008. https://doi.org/10.3892/mmr.2018.9164