| First Author | Wang Y | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 7 | Pages | e0181248 |
| PubMed ID | 28708885 | Mgi Jnum | J:245784 |
| Mgi Id | MGI:5915299 | Doi | 10.1371/journal.pone.0181248 |
| Citation | Wang Y, et al. (2017) Pioglitazone ameliorates glomerular NLRP3 inflammasome activation in apolipoprotein E knockout mice with diabetes mellitus. PLoS One 12(7):e0181248 |
| abstractText | OBJECTIVE: The NLRP3 inflammasome plays an important role in the pathogenesis of inflammation in diabetic nephropathy (DN). Pioglitazone (PIO) has been found to exert an anti-inflammatory effect in patients with diabetes mellitus, but it is still unclear whether PIO exhibits a similar effect in DN. We aimed to explore the effect and underlying mechanism of PIO on DN, as well as investigate if NLRP3 is a pharmacologic target of PIO. METHODS: We divided 48 apolipoprotein E (apoE) (-/-) mice into 4 groups: apoE (-/-), apoE (-/-) with PIO, diabetic apoE (-/-), and diabetic apoE (-/-) with PIO. Wild type male C57BL/6 mice were used as controls (n = 8 per group). After 8 weeks of PIO treatment, we examined the baseline characteristics and metabolic parameters of each group, and we used enzyme-linked immunosorbent assay (ELISA), western blot, and immunohistochemical staining to evaluate the expression levels of advanced glycation end products (AGEs), receptor for advanced glycation end products (RAGE), NLRP3, nuclear factor-kappa B (NF-kappaB), caspase-1, interleukin (IL)-18, and IL-1beta in each group. RESULTS: Compared to the diabetic apoE (-/-) group, PIO treatment decreased blood glucose, cholesterol, serum blood urea nitrogen (BUN), and creatinine levels. It also depressed the glomerular mesangial expansion. PIO down-regulated expression of AGEs, RAGE, and NF-kappaB, all of which further depressed NLRP3, caspase-1, IL-18, and IL-1beta levels. CONCLUSION: Pioglitazone can ameliorate diabetic renal damage, and this effect is related to the inhibition of renal AGE/RAGE axis activation and the down-regulation of NF-kappaB expression. These effects lead to a decline in NLRP3 levels and downstream secretion of inflammatory cytokines. |
