Increased Migratory and Activation Cell Markers of Peripheral Blood Lymphocytes in an Experimental Model of Nephrotic Syndrome

Pereira, Wagner de Fátima; Brito-Melo, Gustavo Eustáquio Alvim; Carneiro, Cláudia Martins; Melo, Dirceu de Sousa; Costa, Karine Beatriz; Guimarães, Fábio Lourenço Tadeu; Rocha‐Vieira, Etel; Vieira, Érica Leandro Marciano; Silva, Ana Cristina Simões e

doi:10.1155/2015/209764

Cited by 6 publications

(6 citation statements)

References 56 publications

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“…Also consistent with previous studies [ 47–49 ], intense lymphocyte infiltration, indicating early activation of adaptive immunity, was observed at the renal interstitial area only 2 weeks after ADR injection. In addition, early activation of at least two major innate immunity pathways was observed in this group: the TLR4/NF-κB/IL-6 pathway and the NLRP3 inflammasome/Caspase-1 pathway, along with IL-1β, one of its most potent end products.…”

Section: Discussionsupporting

confidence: 92%

Simultaneous activation of innate and adaptive immunity participates in the development of renal injury in a model of heavy proteinuria

et al. 2018

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Protein overload of proximal tubular cells (PTCs) can promote interstitial injury by unclear mechanisms that may involve activation of innate immunity. We investigated whether prolonged exposure of tubular cells to high protein concentrations stimulates innate immunity, triggering progressive interstitial inflammation and renal injury, and whether specific inhibition of innate or adaptive immunity would provide renoprotection in an established model of massive proteinuria, adriamycin nephropathy (ADR). Adult male Munich–Wistar rats received a single dose of ADR (5 mg/kg, iv), being followed for 2, 4, or 20 weeks. Massive albuminuria was associated with early activation of both the NF-κB and NLRP3 innate immunity pathways, whose intensity correlated strongly with the density of lymphocyte infiltration. In addition, ADR rats exhibited clear signs of renal oxidative stress. Twenty weeks after ADR administration, marked interstitial fibrosis, glomerulosclerosis, and renal functional loss were observed. Administration of mycophenolate mofetil (MMF), 10 mg/kg/day, prevented activation of both innate and adaptive immunity, as well as renal oxidative stress and renal fibrosis. Moreover, MMF treatment was associated with shifting of M from the M1 to the M2 phenotype. In cultivated NRK52-E cells, excess albumin increased the protein content of Toll-like receptor (TLR) 4 (TLR4), NLRP3, MCP-1, IL6, IL-1β, Caspase-1, α-actin, and collagen-1. Silencing of TLR4 and/or NLRP3 mRNA abrogated this proinflammatory/profibrotic behavior. Simultaneous activation of innate and adaptive immunity may be key to the development of renal injury in heavy proteinuric disease. Inhibition of specific components of innate and/or adaptive immunity may be the basis for future strategies to prevent chronic kidney disease (CKD) in this setting.

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Section: Discussionsupporting

confidence: 92%

Simultaneous activation of innate and adaptive immunity participates in the development of renal injury in a model of heavy proteinuria

et al. 2018

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“…The intense activation of monocytes is a potential role in pathogenesis of kidney damage. 27 Losartan treatment was the reduction of levels of renal transforming growth factor-β (TGF-β) in adriamycin-induced nephropathy. TGF-β can be synthesized by numerous cells including macrophages, T and B lymphocytes fibroblasts, and resident renal cells.…”

Section: Discussionmentioning

confidence: 99%

Treatment with irbesatan may improve slit diaphragm alterations in rats with adriamycin-induced nephropathy

Wang

Wei

et al. 2016

J Renin Angiotensin Aldosterone Syst

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Objective:The study aimed to evaluate the effects of oral administration of irbesartan in adriamycin-induced nephropathy considering laboratory changes, kidney histology, and expression of proteins related to slit diaphragm and cytoskeleton of the podocyte.Methods:The animals were divided into control, model, methylprednisolone (MP), and irbesartan groups. The 24-hour urinary protein and biochemical indicators were determined, and renal pathological changes were observed. The mRNA and protein expression of nephrin, podocin, CD2-associated protein (CD2AP), and desmin in the kidney tissue were analyzed.Results:The urinary protein excretion levels in the MP and irbesartan groups were lower than those in the model group (p<0.01). Electron microscopy showed that fusion of the glomerular foot processes of the rats in the irbesartan group was significantly reduced. The mRNA and protein expression levels of nephrin and podocin in the renal tissue in the MP and irbesartan groups were up-regulated compared with the model group (p<0.05), whereas the mRNA and protein expression levels of CD2AP and desmin were significantly down-regulated (p<0.01).Conclusions:For rats with adriamycin-induced nephropathy, irbesartan could significantly reduce proteinuria. As a possible mechanism, irbesartan may improve the slit diaphragm protein of the glomerular podocyte and stabilize the cytoskeleton of the podocyte.

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“…The pathophysiological mechanisms of idiopathic nephrotic syndrome (INS) support an underlying role for the immune system [1,2]. This hypothesis relies on the fact that the main treatment is based on corticosteroids and studies show different inflammatory profiles in patients with INS [3–6].…”

Section: Introductionmentioning

confidence: 99%

Evidence for a role of angiotensin converting enzyme 2 in proteinuria of idiopathic nephrotic syndrome

Filha

Pinheiro²,

Cordeiro

et al. 2019

Bioscience Reports

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Introduction: Renin angiotensin system (RAS) plays a role in idiopathic nephrotic syndrome (INS). Most studies investigated only the classical RAS axis. Therefore, the aims of the present study were to evaluate urinary levels of RAS molecules related to classical and to counter-regulatory axes in pediatric patients with INS, to compare the measurements with levels in healthy controls and to search for associations with inflammatory molecules, proteinuria and disease treatment. Subjects and methods: This cross-sectional study included 31 patients with INS and 19 healthy controls, matched for age and sex. Patients and controls were submitted to urine collection for measurement of RAS molecules [Ang II, Ang-(1-7), ACE and ACE2] by enzyme immunoassay and cytokines by Cytometric Bead Array. Findings in INS patients were compared according to proteinuria: absent (<150 mg/dl, n = 15) and present (≥150 mg/dl, n = 16). Results: In comparison to controls, INS patients had increased Ang II, Ang-(1-7) and ACE, levels while ACE2 was reduced. INS patients with proteinuria had lower levels of ACE2 than those without proteinuria. ACE2 levels were negatively correlated with 24-h-proteinuria. Urinary concentrations of MCP-1/CCL2 were significantly higher in INS patients, positively correlated with Ang II and negatively with Ang-(1-7). ACE2 concentrations were negatively correlated with IP-10/CXCL-10 levels, which, in turn, were positively correlated with 24-h-proteinuria. Conclusion: INS patients exhibited changes in RAS molecules and in chemokines. Proteinuria was associated with low levels of ACE2 and high levels of inflammatory molecules.

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Increased Migratory and Activation Cell Markers of Peripheral Blood Lymphocytes in an Experimental Model of Nephrotic Syndrome

Cited by 6 publications

References 56 publications

Simultaneous activation of innate and adaptive immunity participates in the development of renal injury in a model of heavy proteinuria

Simultaneous activation of innate and adaptive immunity participates in the development of renal injury in a model of heavy proteinuria

Treatment with irbesatan may improve slit diaphragm alterations in rats with adriamycin-induced nephropathy

Evidence for a role of angiotensin converting enzyme 2 in proteinuria of idiopathic nephrotic syndrome

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