Previous studies demonstrated that ROS-NLRP3 inflammasome signaling activation was involved in the pathogenesis of diabetic nephropathy (DN). Recent research has shown that sweet taste receptors (STRs) are important sentinels of innate immunity. Whether high glucose primes ROS-NLRP3 inflammasome signaling via STRs is unclear. In this study, diabetic mouse model was induced by streptozotocin (STZ) in vivo; mouse glomerular mesangial cells (GMCs) and human proximal tubular cells were stimulated by high glucose (10, 20, and 30 mmol/L) in vitro; STR inhibitor lactisole was used as an intervention reagent to evaluate the role and mechanism of the STRs in the pathogenesis of DN. Our results showed that the expression of STRs and associated signaling components (Gα-gustducin, PLCβ2, and TRPM5) was obviously downregulated under the condition of diabetes in vivo and in vitro. Furthermore, lactisole significantly mitigated the production of intracellular ROS and reversed the high glucose-induced decrease of Ca2+ and the activation of NLRP3 inflammasome signaling in vitro (p < 0.05). These combined results support the hypothesis that STRs could be involved in the activation of ROS-NLRP3 inflammasome signaling in the pathogenesis of DN, suggesting that STRs may act as new therapeutic targets of DN.

Aim. To explore the role of group 2 innate lymphoid cells (ILC2s) in the pathogenesis of renal fibrosis in diabetic kidney disease (DKD). Methods. The proportion of ILC2s and the levels of Th2 cytokines (IL-4, IL-5, and IL-13) in the peripheral blood of normal control subjects (NC) or patients with type 2 diabetes mellitus (DM), early diabetic kidney disease (DKD1), or late diabetic kidney disease (DKD2) were analyzed by flow cytometry and ELISA. The expression of transforming growth factor-β1 (TGF-β1), fibronectin (FN), collagen1, IL-4Rα, and IL-13Rα1 in renal tubular epithelial cells (HK-2) induced by IL-4, IL-13, or high glucose was analyzed by ELISA or qPCR. Results. The proportion of ILC2s and the levels of IL-4, IL-5, and IL-13 were significantly increased in DKD patients and were positively correlated with the severity of DKD (P<0.05). The expression of TGF-β1, FN, and collagen1 was significantly upregulated in HK-2 cells induced by IL-4 or IL-13 (P<0.05). Moreover, the IL-4Rα and IL-13Rα1 mRNA in HK2 cells were increased followed by high glucose alone or combined with IL-4 or IL-13, but the differences were not statistically significant (P>0.05). However, compared with high-glucose stimulation alone, the expression of TGF-β1, FN, and collagen1 was significantly increased in HK-2 cells induced by high glucose combined with IL-4 or IL-13 (P<0.05). Conclusions. ILC2s may participate in renal fibrosis in DKD partly via TGF-β1 signal pathway.