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- W2808172242 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." @default.
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- W2808172242 date "2018-06-14" @default.
- W2808172242 modified "2023-10-10" @default.
- W2808172242 title "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" @default.
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- W2808172242 doi "https://doi.org/10.3892/mmr.2018.9164" @default.
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