Journal
MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 433, Issue C, Pages 75-86Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2016.06.004
Keywords
MiR-451; LMP7; NF-kappa B; Inflammation; Diabetic nephropathy
Categories
Funding
- 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]
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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.
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