Related Experiment Video
Updated: Mar 20, 2026
Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
Published on: August 23, 2024
miR-451 suppresses the NF-kappaB-mediated proinflammatory molecules expression through inhibiting LMP7 in diabetic
Yan Sun1, Rui Peng2, Huimin Peng3
1Molecular Medicine and Cancer Research Center, Chongqing Medical University, No.1 Yixueyuan Road, Yuzhong District, Chongqing 400016, China.
Abstract:
Activation of nuclear factor -kappa B (NF-κB) 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-κB. However, it remained unclear whether miR-451 affected NF-κB-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-κB 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-κB 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-κB central inflammatory pathway during progression of DN.
Insights
MicroRNA-451 (miR-451) is downregulated in diabetic nephropathy (DN). Increasing miR-451 inhibits inflammation by targeting Large Multifunctional Protease 7 (LMP7), reducing nuclear factor-kappa B (NF-κB) activation and kidney damage.
Area of Science:
- Nephrology
- Molecular Biology
- Immunology
Background:
- Nuclear factor-kappa B (NF-κB) activation drives inflammation in diabetic nephropathy (DN) progression.
- MicroRNA-451 (miR-451) is implicated in renal damage in DN.
- Large multifunctional protease 7 (LMP7), an immunoproteasome subunit, activates NF-κB, but its regulation by miR-451 in DN was unclear.
Purpose of the Study:
- To investigate the role of miR-451 in regulating LMP7 and NF-κB-induced inflammation in diabetic nephropathy.
- To elucidate the therapeutic potential of miR-451 in DN.
Main Methods:
- Deep sequencing, in situ hybridization, quantitative real-time PCR.
- Dual-luciferase reporter gene assays, Western blot, and chromatin immunoprecipitation.
- Assessment in db/db mouse models, human peripheral blood mononuclear cells (PBMCs), and cultured mesangial cells (MCs).
Main Results:
- miR-451 was significantly downregulated in DN kidneys, patient PBMCs, and high-glucose-cultured MCs.
- miR-451 directly targets LMP7, inhibiting NF-κB activity and pro-inflammatory molecule transcription in MCs.
- In vivo, enhanced miR-451 suppressed LMP7/NF-κB signaling, reducing urinary microalbumin, blood glucose, and glomerular injury in db/db mice.
Conclusions:
- miR-451 plays a crucial role in regulating the LMP7/NF-κB inflammatory pathway in DN.
- Restoring miR-451 levels offers a potential therapeutic strategy for mitigating DN progression and associated kidney damage.
More Related Videos
07:01Delivery of Exogenous Artificially Synthesized miRNA Mimic to the Kidney Using Polyethylenimine Nanoparticles in Several Kidney Disease Mouse Models
Published on: May 10, 2022
08:15Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease
Published on: May 10, 2024
