| First Author | Sun Y | Year | 2016 |
| Journal | Mol Cell Endocrinol | Volume | 433 |
| Pages | 75-86 | PubMed ID | 27264074 |
| Mgi Jnum | J:248937 | Mgi Id | MGI:6095484 |
| Doi | 10.1016/j.mce.2016.06.004 | Citation | Sun Y, et al. (2016) miR-451 suppresses the NF-kappaB-mediated proinflammatory molecules expression through inhibiting LMP7 in diabetic nephropathy. Mol Cell Endocrinol 433:75-86 |
| abstractText | Activation of nuclear factor -kappa B (NF-kappaB) is associated with inflammation in the progression of diabetic nephropathy (DN). MiR-451 is closely linked to renal damage in DN. Large multifunctional protease 7 (LMP7), an immunoproteasome subunit, can activate NF-kappaB. However, it remained unclear whether miR-451 affected NF-kappaB-induced inflammation by regulating LMP7 in DN. In this study, deep sequencing, in situ hybridization, quantitative real-time PCR, dual-luciferase reporter gene assays, western blot and chromatin immunoprecipitation were respectively used. For the results, we found that miR-451 was markedly downregulated in the kidneys of db/db mice, PBMCs of DN patients and mesangial cells (MCs) cultured in high glucose conditions. Furthermore, miR-451 directly targeted LMP7 expression to inhibit NF-kappaB activity, and down-regulated transcription of proinflammatory molecules in MCs. More importantly, in the kidneys of db/db DN mice, increasing miR-451 level inhibited LMP7/NF-kappaB activity, and attenuated the urinary microalbumin excretion, blood glucose, and glomerular injury. In conclusion, these results provide new insights into the regulation of miR-451 via the LMP7/NF-kappaB central inflammatory pathway during progression of DN. |
