期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 433, 期 C, 页码 75-86出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2016.06.004
关键词
MiR-451; LMP7; NF-kappa B; Inflammation; Diabetic nephropathy
资金
- National Natural Science Foundation of China [81270912]
- project of Science and Technology Commission Foundation of Chongqing Municipality [cstc2013jcyjA10044]
- Scientific Research Foundation of Chongqing Medical University [201420]
Activation of nuclear factor-kappa B (NF-kappa B) 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-kappa B. However, it remained unclear whether miR-451 affected NF-kappa B-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-kappa B 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-kappa B 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-kappa B central inflammatory pathway during progression of DN. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据