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Biological effects of angiotensin II (AngII) such as regulation of AngII target genes may be triggered by interaction of AngII with intracellular AngII receptor types 1 and 2 (AT1 and AT2), defined as intracrine response. The aim of this study was to examine the presence of AT1 and AT2 receptors in nuclear membrane of human mesangial cells (HMCs) and evaluate the possible biological effects mediated by intracellular AT1 through an intracrine mechanism. Subcellular distribution of AT1 and AT2 was evaluated by immunofluorescence and by western blot in isolated nuclear extract. Endogenous intracellular synthesis of AngII was stimulated by high glucose (HG). Effects of HG were analyzed in the presence of candesartan, which prevents AngII internalization. Both receptors were found in nuclear membrane. Fluorescein isothiocyanate (FITC)-labeled AngII added to isolated nuclei produced a fluorescence that was reduced in the presence of losartan or PD-123319 and quenched in the presence of both inhibitors simultaneously. HG induced overexpression of fibronectin and increased cell proliferation in the presence of candesartan, indicating an intracrine action of AngII induced by HG. Results showed the presence of nuclear receptors in HMCs that can be activated by AngII through an intracrine response independent of cytoplasmic membrane AngII receptors.

Background. Chronic renal artery stenosis is considered one of the most common causes of renovascular hypertension (RH). Chronic hypoxia can lead to irreversible damage to renal tissue and to a progressive deterioration of renal function. We have previously shown that bone marrow-derived mesenchymal stem cells (BMSCs) improved renal parenchyma and function in a model of RH (2 kidneys, 1 clip model (2K-1C) in rats. Microvesicles (MVs) and exosomes (EXs) released by MSCs have been shown to induce effects similar to those induced by whole cells but with fewer side effects. In this study, we compared the effects of adipose-derived MSCs (ASCs) with those of the MVs and EXs released by ASCs on tissue inflammation and renal function in 2 K-1C rats. Results. Flow cytometry analysis showed that even after 15 days, ASCs were still detected in both kidneys. The expression of a stem cell homing marker (SDF1-α) was increased in ASC-treated animals in both the stenotic and contralateral kidneys. Interestingly, SDF1-α expression was also increased in MV- and EX-treated animals. A hypoxia marker (HIF1-α) was upregulated in the stenotic kidney, and treatments with ASCs, MVs, and EXs were effective in reducing the expression of this marker. Stenotic animals showed a progressive increase in systolic blood pressure (SBP), while animals treated with ASCs, MVs, and EXs showed a stabilization of SBP, and this stabilization was similar among the different treatments. Stenotic animals developed significant proteinuria, which was reduced by ASCs and MVs but not by EXs. The increased expression of Col I and TGFβ in both kidneys was reduced by all the treatments, and these treatments also effectively increased the expression of the anti-inflammatory cytokine IL-10 in both kidneys; however, only ASCs were able to reduce the overexpression of the proinflammatory cytokine IL-1β in both kidneys of 2K-1C animals. Conclusion. The results of this study demonstrated that the EVs released by ASCs produced beneficial results but with lower efficacy than whole cells. ASCs produced stronger effects in this model of renal chronic hypoxia, and the use of EVs instead of whole cells should be evaluated depending on the parameter to be corrected.

Acute kidney injury is mostly reversible, and hepatocyte growth factor (HGF) has a relevant role in the tissue repair. MicroRNA (miR)-26a is an endogenous modulator of HGF. The role of miR-26a in the kidney repair process was evaluated in Wistar rats submitted to an acute kidney injury model of rhabdomyolysis induced by glycerol (6 mL/kg). Animals were evaluated 3, 12, 48, 96, and 120 hours after glycerol injection. Serum creatinine (SCr) and gene expression of HGF, c-met, signal transducer and activator of transcription 3 (STAT3), and miR-26a were estimated. Also, tubular NK52E cells were transfected with anti-miR26a and stimulated with Fe3+ for 24 hours to mimic the effects of myoglobin in vitro. SCr was highest after 48 hours. After 96 hours, SCr started to decrease, characterizing the recovery phase, with normalization after 120 hours. HGF expression increased during the onset phase (3 hours), with a low relationship with miR-26a. In contrast, in the recovery phase, the increase in miR-26a was coincident with HGF messenger RNA suppression, suggesting that in the recovery phase, miR-26a may have a role in HGF modulation. Fe3+ induced cellular death after 3 hours and proliferation after 24 hours. There was no correlation between miR-26a and STAT3 during the death phase; however, during the proliferation phase, an increase in STAT3 was paralleled with a decrease in miR-26a. miR-26a silencing induced increases in cell viability and the phosphorylated form of STAT3 protein expression in cells receiving Fe3+ . In conclusion, miR-26a may have a key role in modulating HGF levels after its proliferative effects have been triggered.

Biological effects of angiotensin II (AngII) such as regulation of AngII target genes may be triggered by interaction of AngII with intracellular AngII receptor types 1 and 2 (AT

Excess adipose tissue in the body is a prevalent public health problem in many parts of the world. Sedentary lifestyle and obesity are among the risk factors that isolated or associated with other risk behaviors, which increase chance of developing of cancer, type 2 diabetes and cardiovascular diseases and can reduce life expectancy. The purpose of this literature review was to analyze evidences for the effects of obesity, of physical activity and cancer. Were searched English-language Medline and PubMed publications about the involvement of the effects and mechanisms that obesity, comorbidities and sedentary lifestyle may contribute to the development and progression of cancer. Scientific evidence shows that exercise has beneficial effects on disease prevention and has also become an important adjuvant in health promotion. Therefore, imbalances of proinflammatory and anti-inflammatory molecules linked to adipose tissue are positively associated with risk of chronic diseases. Physical exercise used as a therapeutic approach is a strategy that will contribute to primary and secondary prevention of diseases, especially if combined with other therapies that control risk factors for the development of cardiovascular and oncological diseases in overweight or obese individuals.

Obesity and its consequences can damage the kidney over time. However, less is known about the impact of developing overweight/obesity during childhood on the kidney in adulthood and the renal impact of a superimposed acute kidney injury (AKI). This study evaluated the effect of obesity induced by a high-fat diet initiated soon after weaning on the adult life of mice and their response to superimposed nephrotoxic effects of cisplatin. C57BL/6 post-weaning mice (3 weeks old) were divided into a control group (CT, n = 12) and a high-fat diet group (HF, n = 12). After 9 weeks, animals were further divided into the following groups: CT, CT treated with a single dose of cisplatin (CTCis, 20 mg/kg, i.p.), HF and HF treated with cisplatin (HFCis). The HF group exhibited higher body weight gain compatible with a moderate obesity. Obese mice presented increased visceral adiposity, hyperkalemia, sodium retention, glomerular hyperfiltration and proteinuria, without any significant changes in blood pressure and glycemia. AKI induced by cisplatin was exacerbated in obese animals with a 92% reduction in the GFR versus a 31% decrease in the CTCis group; this sharp decline resulted in severely elevated serum creatinine and urea levels. Acute tubular necrosis induced by cisplatin was worsened in obese mice. The HFCis group exhibited robust systemic and intrarenal inflammation that was significantly higher than that in the CTCis group; the HFCis group also showed a higher degree of renal oxidative stress. In conclusion, the moderate degree of obesity induced shortly after weaning resulted in mild early renal alterations, however, obese young animals were prone to develop a much more severe AKI induced by cisplatin.

AB Introduction: Phalaris canariensis L. (Pc), known as birdseed, is rich in tryptophan. The aqueous extract of Pc (AEPc) treatment reduced systolic blood pressure (SBP) in spontaneously hypertensive rats (SHR) via mechanisms mediated by the tryptophan metabolizing enzyme indoleamine 2,3-dioxygenase (IDO). Hypertension is a risk factor to cardiovascular and renal diseases. Considering that physical exercise improves hypertension and cardiovascular function, the aim of this study was to evaluate whether the benefits of exercise (Ex) would be enhanced by concomitant AEPc treatment (400 mg[middle dot]kg-1[middle dot]d-1 p.o.). Methods: Vascular reactivity was assessed in aorta rings from SHR treated with AEPc for 4 wk. Training intensity was based on maximal lactate steady state obtained during the 2-wk adaptation period in a treadmill running. Then exercised (60 min running, five times per week during 8 wk) or sedentary SHR were untreated or treated with AEPc during 8 wk. SBP was estimated by plethysmograph. Heart mass and body mass were used to obtain the index of cardiac hypertrophy. Glucose tolerance test was evaluated by oral glucose overload, and the mRNA expressions of indoleamine 2,3-dioxygenase, interleukin 1[beta] (IL-1[beta]), and IL-10 in the kidney were obtained by real time polymerase chain reaction. Results: AEPc induced endothelial-mediated vascular relaxation. AEPc or Ex alone reduced SBP, the index of cardiac hypertrophy and ventricular fibrosis, improved glucose metabolism, and attenuated proteinuria and the renal expression of the proinflammatory IL-1[beta] with an overexpression in the anti-inflammatory IL-10. AEPc potentiated the benefits of the Ex on the cardiovascular system, metabolic parameters, and renal inflammation. Conclusion: Birdseed reduced cardiovascular risk related to hypertension and had positive effects when associated to physical exercise. (C) 2016 American College of Sports Medicine