NF-kappa B System Is Chronically Activated and Promotes Glomerular Injury in Experimental Type 1 Diabetic Kidney Disease
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Citações na Scopus
30
Tipo de produção
article
Data de publicação
2020
Título da Revista
ISSN da Revista
Título do Volume
Editora
FRONTIERS MEDIA SA
Citação
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.
Palavras-chave
diabetic kidney disease, glomerulosclerosis, NF-kappa B, innate immunity, pyrrolidine dithiocarbamate
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Coleções
Artigos e Materiais de Revistas Científicas - LIM/05
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/16
Artigos e Materiais de Revistas Científicas - ODS/03
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/16
Artigos e Materiais de Revistas Científicas - ODS/03