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https://observatorio.fm.usp.br/handle/OPI/35706
Título: | NF-kappa B System Is Chronically Activated and Promotes Glomerular Injury in Experimental Type 1 Diabetic Kidney Disease |
Autor(es): | FORESTO-NETO, Orestes; ALBINO, Amanda Helen; ARIAS, Simone Costa Alarcon; FAUSTINO, Viviane Dias; ZAMBOM, Fernanda Florencia Fregnan; CENEDEZE, Marcos Antonio; ELIAS, Rosilene Motta; MALHEIROS, Denise Maria Avancini Costa; CAMARA, Niels Olsen Saraiva; FUJIHARA, Clarice Kazue; ZATZ, Roberto |
Parte de: | FRONTIERS IN PHYSIOLOGY, v.11, article ID 84, 11p, 2020 |
Resumo: | High glucose concentration can activate TLR4 and NF-kappa B, triggering the production of proinflammatory mediators. We investigated whether the NF-kappa B pathway is involved in the pathogenesis and progression of experimental diabetic kidney disease (DKD) in a model of long-term type 1 diabetes mellitus (DM). Adult male Munich-Wistar rats underwent DM by a single streptozotocin injection, and were kept moderately hyperglycemic by daily insulin injections. After 12 months, two subgroups - progressors and non-progressors - could be formed based on the degree of glomerulosclerosis. Only progressors exhibited renal TLR4, NF-kappa B and IL-6 activation. This scenario was already present in rats with short-term DM (2 months), at a time when no overt glomerulosclerosis can be detected. Chronic treatment with the NF-kappa B inhibitor, pyrrolidine dithiocarbamate (PDTC), prevented activation of renal TLR4, NF-kappa B or IL-6, without interfering with blood glucose. PDTC prevented the development of glomerular injury/inflammation and oxidative stress in DM rats. In addition, the NF-kappa B p65 component was detected in sclerotic glomeruli and inflamed interstitial areas in biopsy material from patients with type 1 DM. These observations indicate that the renal NF-kappa B pathway plays a key role in the development and progression of experimental DKD, and can become an important therapeutic target in the quest to prevent the progression of human DKD. |
Aparece nas coleções: | Artigos e Materiais de Revistas Científicas - FM/MCM Artigos e Materiais de Revistas Científicas - FM/MPT Artigos e Materiais de Revistas Científicas - HC/ICHC Artigos e Materiais de Revistas Científicas - LIM/05 Artigos e Materiais de Revistas Científicas - LIM/16 Artigos e Materiais de Revistas Científicas - ODS/03 |
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art_FORESTO-NETO_NFkappa_B_System_Is_Chronically_Activated_and_Promotes_2020.PDF | publishedVersion (English) | 4.51 MB | Adobe PDF | Visualizar/Abrir |
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