دورية أكاديمية
Targeting nf-κb by the cell-permeable nemo-binding domain peptide improves albuminuria and renal lesions in an experimental model of type 2 diabetic nephropathy
| العنوان: | Targeting nf-κb by the cell-permeable nemo-binding domain peptide improves albuminuria and renal lesions in an experimental model of type 2 diabetic nephropathy |
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| المؤلفون: | Opazo-Ríos, Lucas, Plaza, Anita, Matus, Yenniffer Sánchez, Bernal, Susana, Lopez-Sanz, Laura, Jimenez-Castilla, Luna, Carpio, Daniel, Droguett, Alejandra, Mezzano, Sergio, Egido, Jesús, Gómez Guerrero, Carmen |
| المساهمون: | UAM. Departamento de Medicina, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD) |
| بيانات النشر: | MDPI, Basel, SMwitzerland |
| سنة النشر: | 2021 |
| المجموعة: | Universidad Autónoma de Madrid (UAM): Biblos-e Archivo |
| مصطلحات موضوعية: | Albuminuria, BTBR ob/ob mice, Diabetic nephropathy, Inflammation, NF-κB pathway, Medicina |
| الوصف: | Diabetic nephropathy (DN) is a multifactorial disease characterized by hyperglycemia and close interaction of hemodynamic, metabolic and inflammatory factors. Nuclear factor-κB (NF-κB) is a principal matchmaker linking hyperglycemia and inflammation. The present work investigates the cell-permeable peptide containing the inhibitor of kappa B kinase γ (IKKγ)/NF-κB essential modulator (NEMO)-binding domain (NBD) as therapeutic option to modulate inflammation in a preclinical model of type 2 diabetes (T2D) with DN. Black and tan, brachyuric obese/obese mice were randomized into 4 interventions groups: Active NBD peptide (10 and 6 µg/g body weight); Inactive mutant peptide (10 µg/g); and vehicle control. In vivo/ex vivo fluorescence imaging revealed efficient delivery of NBD peptide, systemic biodistribution and selective renal metabolization. In vivo administration of active NBD peptide improved albuminuria (>40% reduction on average) and kidney damage, decreased podocyte loss and basement membrane thickness, and modulated the expression of proinflammatory and oxidative stress markers. In vitro, NBD blocked IKK-mediated NF-κB induction and target gene expression in mesangial cells exposed to diabetic-like milieu. These results constitute the first nephroprotective effect of NBD peptide in a T2D mouse model that recapitulates the kidney lesions observed in DN patients. Targeting IKK-dependent NF-κB activation could be a therapeutic strategy to combat kidney inflammation in DN. ; This work was supported by grants from: Fondecyt Project No 1160465 to S.M. and PhD CONICYT Grant No 21150768 to L.O-R.; Spanish Ministry of Economy and Competitiveness (MINECO/FEDER; SAF2015-63696-R to C.G-G.), Ministry of Science and Innovation (MICINN/FEDER; RTI2018-098788-B-1I00 to C.G-G.) and Instituto de Salud Carlos III (FIS/FEDER; PI17/01495 and DTS-2017/00203 to J.E.) |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1661-6596 |
| العلاقة: | International Journal of Molecular Sciences; http://doi.org/10.3390/ijms21124225Test; Gobierno de España. PI17/01495; Gobierno de España. DTS-2017/00203; International Journal of Molecular Sciences 21.12 (2020): 4225; http://hdl.handle.net/10486/695184Test; 4225-1; 12; 4225-17; 21 |
| DOI: | 10.3390/ijms21124225 |
| الإتاحة: | https://doi.org/10.3390/ijms21124225Test http://hdl.handle.net/10486/695184Test |
| حقوق: | © 2020 The Authors ; Reconocimiento ; openAccess |
| رقم الانضمام: | edsbas.23988A89 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 16616596 |
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| DOI: | 10.3390/ijms21124225 |