Liver up-regulation of ADAMTS13 gene expression and its correlation with renal markers in mice with type 1 diabetes mellitus and nephropathy
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Universidade Federal de Minas Gerais
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Artigo de periódico
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Membros da banca
Resumo
Diabetic nephropathy (DN) is one of the most important risk factors for cardiovascular disease (CVD), contributing to approximately 45% of end stage renal disease (ESRD) cases [1]. The hypercoagulability state in diabetes results from the imbalance between pro- and anti-coagulant proteins, which leads to thrombotic events [2].
ADAMTS13 (A Desintegrin And Metalloprotease with ThromboSpondin type 1 motifs, member 13) is the physiological von Willebrand factor (VWF) cleavage protease. This protease is synthesized primarily in the human liver, particularly in hepatic stellate cells (HSCs), but also in platelet, endothelial cells, kidney and other tissues [3]. VWF glycoprotein plays a central role in the blood coagulation system, acting as the major mediator of platelet-vessel wall interaction and platelet adhesion. Ultra large VWF multimers (UL-VWF) are cleaved by ADAMTS13 under fluid shear stress. When ADAMTS13 is deficient, the UL-VWF lead to platelet aggregation and thrombus formation [4].
In diabetic patients, high VWF levels in the presence of albuminuria have been associated with vasculopathy and CVD [5]. Moreover, decreased ADAMTS13 activity/ADAMTS13 antigen levels ration have been associated with renal injury [1]. These findings lead to the hypothesis that ADAMTS13 antigen levels may be affected in patients with nephropathy, although it remains unclear the mechanism underlying altered levels of these proteins in diabetes. Therefore, we investigated, in a type 1 diabetes mellitus (T1DM) animal model, how renal injury may influence the ADAMTS13 antigen levels, by measuring urinary and plasma levels of ADAMTS13 antigen and its gene expression in kidney and liver tissues.
Abstract
Assunto
Diabetes
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Fígado, Marcadores renais, Diabetes, Nefropatia
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https://www.sciencedirect.com/science/article/pii/S0049384817304371