Please use this identifier to cite or link to this item: https://observatorio.fm.usp.br/handle/OPI/3098
Title: VITAMIN D DEFICIENCY IS ASSOCIATED WITH DOWNREGULATION OF KLOTHO AND DEVELOPMENT OF FIBROSIS IN A MURINE MODEL OF RENAL ISCHEMIA/REPERFUSION INJURY
Authors: GONCALVES, Janaina G.CANALE, DanieleBRAGANCA, Ana Carolina deSHIMIZU, Maria Heloisa M.MOYSES, Rosa Maria A.ANDRADE, LuciaSEGURO, Antonio C.VOLPINI, Rildo A.
Citation: NEPHROLOGY DIALYSIS TRANSPLANTATION, v.28, suppl.1, p.186-186, 2013
Abstract: Introduction and Aims:Vitamin D deficiency (VDD) is highly prevalent in chronic kidney disease (CKD) patients. Ischemia/reperfusion-Acute Kidney Injury (IR-AKI) is considered a risk factor for CKD progression. Previous studies suggests that activation of the renin-angiotensin-aldosterone system (RAAS) and VDD could be involved in reduction of Klotho expression, an early marker of stage 1 CKD. The aim of this study was to investigate the effect of VDD on klotho expression and fibrosis development in a model of IR-AKI. Methods:Male Wistar rats (180-200g) were randomly divided into four groups (n=8 each): control (C) and ischemic (IR) fed a standard diet; VDD and VDD+IR, fed a free-vitamin D diet. On day 28, IR and VDD+IR rats were submitted to 45-minute clamping of both renal arteries. On day 90, we measured inulin clearance (GFR); Mean arterial blood pressure (MAP), renal blood flow (RBF) and calculated renal vascular resistance (RVR). We also measured serum levels of 25-hydroxyvitamin D (25(OH)D, ng/mL) and proteinuria. In renal tissue, we immunoblotted for klotho and performed imunohistochemical assay for collagen IV and fibronectin. We estimated fibrosis by fractional interstitial area (FIA) and fibronectin/collagen IV expression by score ranging from 0 to 4 according to the extension of staining. Data are expressed as mean ± SEM. Table 1. Hemodynamic and biochemical data and fractional interstitial area, Western Blot and Immunohistochemical studies. Results:Vitamin D levels were similar in C (15.4±1) and IR (15±0.6) groups and <1.5 ng/mL in VDD groups. GFR, RBF and RVR were not different among the studied groups. MAP was markedly elevated in VDD, IR and VDD+IR groups, reflecting a possible interaction on RAAS. Also, VDD, IR and VDD+IR groups showed larger areas of fibrosis and higher scores for fibronectin and collagen IV and decreased levels of klotho. Conclusions:The increased proteinuria/fibrosis and fibronectin/collagen IV expression in VDD+IR rats suggests progressive renal injury. Downregulation of klotho expression is a possible marker of chronification. Our study shows a very plausible role of VDD in this pathway as a potential stimulus for fibrosis.
Appears in Collections:

Comunicações em Eventos - FM/MCM
Departamento de Clínica Médica - FM/MCM

Comunicações em Eventos - HC/ICHC
Instituto Central - HC/ICHC

Comunicações em Eventos - LIM/12
LIM/12 - Laboratório de Pesquisa Básica em Doenças Renais

Comunicações em Eventos - LIM/16
LIM/16 - Laboratório de Fisiopatologia Renal


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