Introduction: Diabetic nephropathy (DN) is a serious complication of diabetes mellitus and is considered to be a sterile inflammatory disease. Increasing evidence suggest that pyroptosis and subsequent inflammatory response play a key role in the pathogenesis of DN. However, the underlying cellular and molecular mechanisms responsible for pyroptosis in DN are largely unknown.
Methods: The rat models of DN were successfully established by single 65 mg/kg streptozotocin treatment. Glomerular mesangial cells were exposed to 30 mmol/L high glucose media for 48 h to mimic the DN environment in vitro. Gene and protein expressions were determined by quantitative real-time PCR and Western blot. Cell viability and pyroptosis were measured by MTT assay and flow cytometry analysis, respectively. The relationship between lncRNA NEAT1, miR-34c, and Nod-like receptor protein-3 (NLRP3) was confirmed by luciferase reporter assay.
Results: We found that upregulation of NEAT1 was associated with the increase of pyroptosis in DN models. miR-34c, as a target gene of NEAT1, mediated the effect of NEAT1 on pyroptosis in DN by regulating the expression of NLRP3 as well as the expressions of caspase-1 and interleukin-1β. Either miR-34c inhibition or NLRP3 overexpression could reverse the accentuation of pyroptosis and inflammation by sh-NEAT1 transfection in the in vitro model of DN.
Conclusions: Our findings suggested NEAT1 and its target gene miR-34c regulated cell pyroptosis via mediating NLRP3 in DN, providing new insights into understanding the molecular mechanisms of pyroptosis in the pathogenesis of DN.
Keywords: Inflammation; NEAT1; NLRP3; Pyroptosis; miR-34c.
© 2020 The Author(s) Published by S. Karger AG, Basel.