Renin-angiotensin system may trigger kidney damage in NOD mice

Colucci, Juliana Almada; Arita, Danielle Yuri; Cunha, Tatiana Sousa; Marco, Giovana Seno Di; Vio, Carlos P.; Pacheco-Silva, Álvaro; Casarini, Dulce Elena

doi:10.1177/1470320310375456

Cited by 18 publications

(12 citation statements)

References 48 publications

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“…We found that ACE activity was decreased in heart from DB mice, but only at early stage. However, in previous studies by Colucci and co-authors, there were no differences between control and diabetic mice [12]. In all studied tissues, the insulin-treated group presented no significant differences compared to the non-treated diabetic group.…”

Section: Discussioncontrasting

confidence: 50%

“…Later on, its elements were also found in extrarenal tissues, indicating the presence of a local paracrine system that coexists with the circulating RAS [8]. Thus, ACE expression was mainly found in the surface of endothelial cells of lungs, renal brush border membranes, intestines, choroid plexus, placenta [9,10,11], and, to a lesser extent, in cardiac, hepatic, pancreatic, and adrenal tissues [12]. In contrast, ACE2 protein expression was initially reported to be more tissue restricted and higher than ACE, being described preferentially in kidneys (renal tubules and glomeruli), heart, and testis [13].…”

Section: Introductionmentioning

confidence: 99%

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Characterization of ACE and ACE2 Expression within Different Organs of the NOD Mouse

Roca-Ho

Riera

Palau

et al. 2017

IJMS

251

212

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Renin angiotensin system (RAS) is known to play a key role in several diseases such as diabetes, and renal and cardiovascular pathologies. Its blockade has been demonstrated to delay chronic kidney disease progression and cardiovascular damage in diabetic patients. In this sense, since local RAS has been described, the aim of this study is to characterize angiotensin converting enzyme (ACE) and ACE2 activities, as well as protein expression, in several tissues of the non-obese diabetic (NOD) mice model. After 21 or 40 days of diabetes onset, mouse serums and tissues were analyzed for ACE and ACE2 enzyme activities and protein expression. ACE and ACE2 enzyme activities were detected in different tissues. Their expressions vary depending on the studied tissue. Thus, whereas ACE activity was highly expressed in lungs, ACE2 activity was highly expressed in pancreas among the studied tissues. Interestingly, we also observed that diabetes up-regulates ACE mainly in serum, lung, heart, and liver, and ACE2 mainly in serum, liver, and pancreas. In conclusion, we found a marked serum and pulmonary alteration in ACE activity of diabetic mice, suggesting a common regulation. The increase of ACE2 activity within the circulation in diabetic mice may be ascribed to a compensatory mechanism of RAS.

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Section: Discussioncontrasting

confidence: 50%

Section: Introductionmentioning

confidence: 99%

Characterization of ACE and ACE2 Expression within Different Organs of the NOD Mouse

Roca-Ho

Riera

Palau

et al. 2017

IJMS

251

212

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“…Colucci et al found decreased ACE2 protein expresion in kidney cortex from Diabetic mice, however, these authors did not measure ACE2 enzymatic activity. Also in Colucci study animal age and diabetes duration is not stated, whereas in our study animals were followed for 21 and 40 days after the diagnosis of diabetes [32]. Thus, it is possible that differences in ACE2 protein content between both studies reflect differences in age and disease evolution over time.…”

Section: Discussionmentioning

confidence: 77%

Effect of Insulin on ACE2 Activity and Kidney Function in the Non-Obese Diabetic Mouse

et al. 2014

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We studied the non-obese diabetic (NOD) mice model because it develops autoimmune diabetes that resembles human type 1 diabetes. In diabetic mice, urinary albumin excretion (UAE) was ten-fold increased at an “early stage” of diabetes, and twenty-fold increased at a “later stage” (21 and 40 days, respectively after diabetes diagnosis) as compared to non-obese resistant controls. In NOD Diabetic mice, glomerular enlargement, increased glomerular filtration rate (GFR) and increased blood pressure were observed in the early stage. In the late stage, NOD Diabetic mice developed mesangial expansion and reduced podocyte number. Circulating and urine ACE2 activity were markedly increased both, early and late in Diabetic mice. Insulin administration prevented albuminuria, markedly reduced GFR, blood pressure, and glomerular enlargement in the early stage; and prevented mesangial expansion and the reduced podocyte number in the late stage of diabetes. The increase in serum and urine ACE2 activity was normalized by insulin administration at the early and late stages of diabetes in Diabetic mice. We conclude that the Diabetic mice develops features of early kidney disease, including albuminuria and a marked increase in GFR. ACE2 activity is increased starting at an early stage in both serum and urine. Moreover, these alterations can be completely prevented by the chronic administration of insulin.

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“…Although some studies describe an increase in ACE2 mRNA levels and protein expression in diabetes [ 47 ], Reich et al (2008) described a decrease in the same parameters in renal biopsies of patients with kidney disease due to diabetes [ 57 ] and Colucci et al (2011) showed a decrease in ACE2 protein expression in the kidney from D-NOD mice [ 58 ]. We believe that these differences are related to diabetes duration, and as the progression of disease and DN, the RAS cannot compensate the imbalance on RAS anymore.…”

Section: Resultsmentioning

confidence: 99%

Diabetic Nephropathy Induced by IncreasedAceGene Dosage Is Associated with High Renal Levels of Angiotensin (1–7) and Bradykinin

Bertoncello

Moreira

Arita

et al. 2015

Journal of Diabetes Research

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Population studies have shown an association between diabetic nephropathy (DN) and insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene (ACE in humans, Ace in mice). The aim was to evaluate the modulation of Ace copies number and diabetes mellitus (DM) on renal RAS and correlate it with indicators of kidney function. Increased number of copies of the Ace gene, associated with DM, induces renal dysfunction. The susceptibility to the development of DN in 3 copies of animals is associated with an imbalance in activity of RAS enzymes leading to increased synthesis of Ang II and Ang-(1–7). Increased concentration of renal Ang-(1–7) appears to potentiate the deleterious effects triggered by Ang II on kidney structure and function. Results also show increased bradykinin concentration in 3 copies diabetic group. Taken together, results indicate that the deleterious effects described in 3 copies diabetic group are, at least in part, due to a combination of factors not usually described in the literature. Thus, the data presented here show up innovative and contribute to understanding the complex mechanisms involved in the development of DN, in order to optimize the treatment of patients with this complication.

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Renin-angiotensin system may trigger kidney damage in NOD mice

Cited by 18 publications

References 48 publications

Characterization of ACE and ACE2 Expression within Different Organs of the NOD Mouse

Characterization of ACE and ACE2 Expression within Different Organs of the NOD Mouse

Effect of Insulin on ACE2 Activity and Kidney Function in the Non-Obese Diabetic Mouse

Diabetic Nephropathy Induced by IncreasedAceGene Dosage Is Associated with High Renal Levels of Angiotensin (1–7) and Bradykinin

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