[No authors listed]
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 câJun Nâterminal kinase (JNK) on the NLRP3 inflammasome were examined in vivo and in vitro. SpragueâDawley 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 inflammasomeâassociated proteins following treatment with a Syk inhibitor or Sykâsmall interfering (si)RNA in a high glucose condition. In the present study, it was revealed that the protein and mRNA expression levels of NLRP3 inflammasomeâassociated molecules and the downstream mature interleukin (IL)â1β were upregulated in vivo and in vitro. The Syk inhibitor and SykâsiRNA suppressed high glucoseâinduced JNK activation, and subsequently downregulated the activation of the NLRP3 inflammasome and mature ILâ1β in HK2 cells and RGMCs. Furthermore, high glucoseâinduced apoptosis of HK2 cells was reduced by the Syk inhibitor BAY61â3606. Therefore, the present results determined that high glucoseâinduced activation of the NLRP3 inflammasome is mediated by Syk/JNK activation, which subsequently increased the protein expression level of ILâ1β and mature ILâ1β. The present study identified that the Syk/JNK/NLRP3 signaling pathway may serve a vital role in the pathogenesis of DN.
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