João B Pesquero

Universidade Federal de São Paulo, San Paulo, São Paulo, Brazil

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Publications (211)855.51 Total impact

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    ABSTRACT: Kinins are vasoactive peptides involved in endothelial function and vascular tonus. The present study determined the influence of the kinin B1 receptor subtype on endothelial nitric oxide (NO) metabolism by using primary cultured cells obtained from B1 knockout (B1-/-) and Wild Type (WT) mice. By using specific fluorescent dyes, NO and superoxide anion (O2•) production was determined in absence or presence of ascorbate or tetrahydrobiopterin (BH4). The activity of the enzyme superoxide dismutase (SOD) was determined by immune enzyme assay, and endothelial NOS (eNOS) activation was analyzed through expression of phospho-eNOS (p-eNOS, Ser1177) by western blot. The NO release [quantified by densitometry and expressed as arbitrary units (a.u.)] was markedly reduced in B1-/- (35.8± 3.1* a.u.) when compared toWT cells (66.9± 3.2 a.u.); this impaired response was reversed by ascorbate (101.8± 6.0 a.u.) and BH4 (54.3± 1.7 a.u.). B1-/- cells showed a marked increase in O2• production (77.1± 2.5* a.u.) versus WT (29.3± 6.9 a.u.), which was reversed by ascorbate (35.3± 6.4 a.u.), but not by BH4. SOD activity was similar between groups, and B1-/- cells presented a significant reduction in the expression of p-eNOS. In conclusion, the reduced NO availability detected in B1-/- cells appears to be related to a recurrent process involving BH4 oxidation, NOS uncoupling and further enhancement of NOS-derived O2•. B1 receptor deletion also impairs the phosphorylation of eNOS at the Ser1177 residue, contributing to the deficient NO production at the endothelial level.
    International Journal of Peptide Research and Therapeutics 06/2015; 21(2):135. DOI:10.1007/s10989-015-9466-8 · 0.83 Impact Factor
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    ABSTRACT: The effects of kinin B1 receptor (B1 R) deletion were examined on femur bone regeneration in streptozotocin (STZ)-type 1 diabetes. Diabetes induction in wild-type C57/BL6 (WTC57BL6) mice led to decrease in body weight and hyperglycemia, compared to the non-diabetic group of the same strain. The lack of B1 R did not affect STZ-elicited body weight loss, but partially prevented hyperglycemia. Diabetic mice had a clear delay in bone regeneration, and displayed large areas of loose connective tissue within the defects, with a reduced expression of the mineralization-related protein osteonectin, when compared to the non-diabetic WTC57/BL6. The non-diabetic and diabetic B1 R knockout (B1 RKO) mice had bone regeneration levels and osteonectin expression comparable to that seen in control WTC57/BL6 mice. WTC57/BL6 STZ-diabetic mice also showed a marked reduction of collagen contents, with increased immunolabelling for the apoptosis marker caspase-3, whereas diabetic B1 RKO had collagen levels and caspase-3 activity comparable to those observed in non-diabetic WTC57/BL6 or B1 RKO mice. No significant difference was detected in the number of tartrate-resistant acid phosphatase (TRAP)-stained cells, or in RANK/RANKL/OPG system immunolabelling throughout the experimental groups. Data bring novel evidence on the relevance of kinin B1 R under type 1 diabetes with regards to its role in bone regeneration. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Journal of Cellular Physiology 05/2015; DOI:10.1002/jcp.25034 · 3.87 Impact Factor
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    ABSTRACT: We have investigated early programming of body mass in order to understand the multifactorial etiology of obesity. Considering that the renin-angiotensin system is expressed and functional in the white adipose tissue (WAT) and modulates its development, we reasoned whether early transitory inhibition of angiotensin-I converting enzyme activity after birth could modify late body mass development. Therefore, newborn Wistar rats were treated with enalapril (10 mg/kg of body mass) or saline, starting at the first day of life until the age of 16 days. Between days 90th and 180th, a group of these animals received high fat diet (HFD). Molecular, biochemical, histological and physiological data were collected. Enalapril treated animals presented hyperphagia, overweight and increased serum level of triglycerides, total cholesterol and leptin, in adult life. Body composition analyses revealed higher fat mass with increased adipocyte size in these animals. Molecular analyses revealed that enalapril treatment increases neuropeptide Y (NPY) and cocaine- and amphetamine-regulated transcript (CART) gene expression in hypothalamus, fatty acid synthase (FAS) and hormone-sensitive lipase (HSL) gene expression in retroperitoneal WAT and decreases peroxixome proliferators-activated receptor (PPAR) γ, PPARα, uncoupling protein (UCP) 2 and UCP3 gene expression in WAT. The results of the current study indicate that enalapril administration during early postnatal development increases body mass, adiposity and serum lipids in adulthood associated with enhanced food intake and decreased metabolic activity in WAT, predisposing to obesity in adulthood.
    Frontiers in Pharmacology 04/2015; 6. DOI:10.3389/fphar.2015.00075
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    ABSTRACT: The alpha-actinin-3 r577x polymorphism (rs1815739) is one of the most important polymorphisms associated with athletic performance. This single-nucleotide mutation leads to a premature stop codon, resulting in a nonfunctional protein product. The presence of the dominant R allele is associated with full power skeletal muscle contraction. Homozygosity for the X allele is correlated with more efficient energy disposure. Restriction fragment length polymorphism and real-time polymerase chain reaction (PCR) are the standard methods used to genotype this polymorphism, but they are expensive and require special equipments. Here, we present a simple and cost-efficient method to genotype the ACTN3 r577x polymorphism by a single PCR. External primers yield a 690-bp product that indicates the template quality. Internal primers produce a 413-bp product if the R allele is present and a 318-bp product if the X allele is present. Our four-primer genotyping PCR was validated by the standard real-time PCR, generally used to genotype this single-nucleotide polymorphism, demonstrating the accuracy of this method. This protocol is perfect for small- or large-scale cohort genotyping of the ACTN3 r577x polymorphism.
    Genetic Testing and Molecular Biomarkers 04/2015; 19(5). DOI:10.1089/gtmb.2014.0299 · 1.15 Impact Factor
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    ABSTRACT: Pompe disease is an autosomal recessive disorder linked to GAA gene that leads to a multi-system intralysosomal accumulation of glycogen. Mutation identification in the GAA gene can be very important for early diagnosis, correlation between genotype-phenotype and therapeutic intervention. For this purpose, peripheral blood from 57 individuals susceptible to Pompe disease was collected and all exons of GAA gene were amplified; the sequences and the mutations were analyzed in silico to predict possible impact on the structure and function of the human protein. In this study, 46 individuals presented 33 alterations in GAA gene sequence, among which five (c.547-67C>G, c.547-39T>G, p.R437H, p.L641V and p.L705P) have not been previously described in the literature. The alterations in the coding region included 15 missense mutations, three nonsense mutations and one deletion. One insertion and other 12 single base changes were found in the non-coding region. The mutation p.G611D was found in homozygosis in a one-year-old child, who presented low levels of GAA activity, hypotonia and hypertrophic cardiomyopathy. Two patients presented the new mutation p.L705P in association with c.-32-13T>G. They had low levels of GAA activity and developed late onset Pompe disease. In our study, we observed alterations in the GAA gene originating from Asians, African-Americans and Caucasians, highlighting the high heterogeneity of Brazilian population. Considering that Pompe disease studies are not very common in Brazil, this study will help to better understand the potential pathogenic role of each change in the GAA gene. Furthermore, a precise and early molecular analysis improves genetic counseling besides allowing for a more efficient treatment in potential candidates. Copyright © 2015. Published by Elsevier B.V.
    Gene 02/2015; DOI:10.1016/j.gene.2015.02.023 · 2.08 Impact Factor
  • Molecular Genetics and Metabolism 02/2015; 114(2):S67-S68. DOI:10.1016/j.ymgme.2014.12.144 · 2.83 Impact Factor
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    ABSTRACT: Verify the role of the kinin B1 receptors (B1R) and the effect of ACE inhibitors (ACEi) on acute gout induced by monosodium urate (MSU) crystals in rodents.
    Annals of the Rheumatic Diseases 10/2014; DOI:10.1136/annrheumdis-2014-205739 · 9.27 Impact Factor
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    ABSTRACT: Several deleterious effects may occur when intense and exhaustive exercise (IE) is not well-planned. This study aimed to investigate the effects of a short duration IE on body chemical composition and hypothalamic-pituitary-adrenal (HPA) axis. C57Bl/6 mice were distributed into four groups (10 mice per group): control (C-4D and C-10D), 4 days (E-4D), and 10 days of IE (E-10D). IE program consisted of a daily running session at 85 % of maximum speed until the animal reached exhaustion. Body weight as well as total body water, fat and protein content were determined from animal carcasses. HPA activation was assessed by plasma corticosterone levels measured by radioimmunoassay and the weight of both the adrenal glands and thymus. Plasma corticosterone levels increased by 64 % in both the E-4D and E-10D groups. The weight of the adrenal glands augmented by 74 % and 45 %, at 4 and 10 days of IE, respectively, whereas thymus weight diminished by 15 % only in the E-10D group. Total carcass fat content decreased by 20 % only at 4 days IE, whereas protein content decreased by 20 % in both E-4D and E-10D groups. A relationship between corticosterone plasma levels and loss of body protein content in both E-4D and E-10D groups was observed (R(2)=0.999). We concluded that IE may be related to HPA axis activation associated with remodeling of body chemical composition in C57BL/6 mice.
    Physiological research / Academia Scientiarum Bohemoslovaca 06/2014; · 1.49 Impact Factor
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    ABSTRACT: The current dominance of African runners in long-distance running is an intriguing phenomenon that highlights the close relationship between genetics and physical performance. Many factors in the interesting interaction between genotype and phenotype (eg, high cardiorespiratory fitness, higher hemoglobin concentration, good metabolic efficiency, muscle fiber composition, enzyme profile, diet, altitude training, and psychological aspects) have been proposed in the attempt to explain the extraordinary success of these runners. Increasing evidence shows that genetics may be a determining factor in physical and athletic performance. But, could this also be true for African long-distance runners? Based on this question, this brief review proposed the role of genetic factors (mitochondrial deoxyribonucleic acid, the Y chromosome, and the angiotensin-converting enzyme and the alpha-actinin-3 genes) in the amazing athletic performance observed in African runners, especially the Kenyans and Ethiopians, despite their environmental constraints.
    Open Access Journal of Sports Medicine 05/2014; 5:123-127. DOI:10.2147/OAJSM.S61361
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    ABSTRACT: Focal and segmental glomerulosclerosis (FSGS) is one of the most important renal diseases related to end stage renal failure. Bradykinin has been implicated in the pathogenesis of renal inflammation whereas the role of its receptor 2 (B2RBK) in FSGS has not been studied. FSGS was induced in wild type and B2RBK KO mice by a single intravenous injection of Adriamycin (ADM). In order to further modulate the kinin receptors, animals were also treated with B2RBK antagonist HOE-140, and DALBK, B1RBK antagonist. Here, we show that the blockage of B2RBK with HOE-140 protects mice from FSGS development, including podocyte foot process effacement and reestablishment of slit diaphragm-related proteins. However, B2RBK KO mice were not protected from FSGS. These opposite results were due to B1RBK expression. B1RBK was up regulated after ADM injection and it was exacerbated in B2RBK KO animals. Further, HOE-140 treatment down regulated B1RBK receptor. The blockade of B1RBK in B2RBK KO animals promoted FSGS regression, with a less inflammatory phenotype. These results indicate a deleterious role of both kinin receptors in FSGS model and suggest a possible crosstalk of them in disease progression.
    Disease Models and Mechanisms 04/2014; DOI:10.1242/dmm.014548 · 5.54 Impact Factor
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    ABSTRACT: Regulation of muscle mass depends on the balance between synthesis and degradation of proteins, which is under control of different signaling pathways regulated by hormonal, neural and nutritional stimuli. Such stimuli are altered in several pathologies such as chronic obstructive pulmonary disease, diabetes, AIDS and cancer (cachexia), as well as in some conditions such as immobilization and aging (sarcopenia), leading to muscle atrophy, which represents a significant contribution to patient morbidity. The kallikrein-kinin system (KKS) is composed of the enzymes kallikreins, which generate active peptides called kinins that activate two G protein-coupled receptors, namely B1 and B2, expressed in a variety of tissues. The local modulation of the KKS may account for its described participation in different diseases, such as those of cardiovascular, renal and central nervous systems, cancer, and many inflammatory processes, including pain. Due to such pleiotropic actions of the KKS by local modulatory events and the probable fine-tuning of associated signaling cascades involved in skeletal muscle catabolic disorders (e.g. NFкB and PI3K/Akt pathways), we hypothesized that KKS could contribute to modulation of intracellular responses in atrophying skeletal muscle. Our data showed that the kinin B1 receptor activation induced a decrease in C2C12 myotubes diameters, activation of NFκB, decrease of Akt phosphorylation levels, and increase in the ubiquitin E3 ligases atrogin-1 and MuRF-1 mRNAs levels. In vivo, we observed an increase of the B1 receptor mRNA levels in an androgen-sensitive model of muscle atrophy. In the same model, blockage of the B1 receptor with a selective antagonist resulted in impairment of atrogin-1 and MuRF-1 expression and IκB phosphorylation. Moreover, knockout of B1 receptor in mice led to an impairment of MuRF-1 mRNA expression after induction of levator ani muscle atrophy. As a conclusion, using pharmacological and gene ablation tools, we have obtained evidence that the B1 receptor plays a significant role in regulation of skeletal muscle proteolysis in the model of levator ani muscle atrophy.
    Clinical Science 02/2014; DOI:10.1042/CS20130358 · 5.63 Impact Factor
  • Molecular Cancer Therapeutics 01/2014; 12(11_Supplement):C289-C289. DOI:10.1158/1535-7163.TARG-13-C289 · 6.11 Impact Factor
  • Biophysical Journal 01/2014; 106(2):305a. DOI:10.1016/j.bpj.2013.11.1770 · 3.83 Impact Factor
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    ABSTRACT: Cisplatin is a chemotherapeutic agent that causes severe renal dysfunction. The kinin B1 receptor has been associated with the migration of immune cells to injured tissue as well as with renal inflammation. To examine the role of the kinin B1 receptor in cisplatin-induced acute kidney injury, we used kinin B1 receptor knockout mice and treatment with a receptor antagonist before and after cisplatin administration. Cisplatin injection caused exacerbation of renal macrophage and neutrophil migration, higher levels of serum creatinine and blood urea, upregulation of B1 receptor mRNA and an increase in pro-inflammatory cytokines expression. B1 receptor knockout mice exhibited a reduction in serum creatinine and blood urea levels, diminished apoptosis, and decreased cisplatin-induced upregulation of inflammatory components. Moreover, treatment with the B1 receptor antagonist prior to cisplatin administration normalized serum creatinine, blood urea levels, protected from acute tubular necrosis, apoptosis-related genes, and prevented upregulation of pro-inflammatory cytokines. Thus, we propose that kinins have an important role in cisplatin-induced acute kidney injury by impairing immune cells migration to renal tissue during cisplatin nephrotoxicity. Kinin B1 receptor is upregulated after cisplatin exposure. Kinin B1 receptor deficiency diminishes the nephrotoxicity caused by cisplatin. Kinin B1 receptor deficiency ameliorates the inflammatory response. Kinin B1 receptor deficiency diminishes apoptosis caused by cisplatin. Kinin B1 receptor antagonism ameliorates renal function after cisplatin injection.
    Journal of Molecular Medicine 12/2013; DOI:10.1007/s00109-013-1116-z · 4.74 Impact Factor
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    ABSTRACT: Melanoma is a very aggressive tumor that does not respond well to standard therapeutic approaches, such as radio- and chemotherapies. Furthermore, acquiring the ability to metastasize in melanoma and many other tumor types is directly related to incurable disease. The B1 kinin receptor participates in a variety of cancer-related pathophysiological events, such as inflammation and angiogenesis. Therefore, we investigated whether this G protein-coupled receptor plays a role in tumor progression. We used a murine melanoma cell line that expresses the kinin B1 receptor and does not express the kinin B2 receptor to investigate the precise contribution of activation of the B1 receptor in tumor progression and correlated events using various in vitro and in vivo approaches. Activation of the kinin B1 receptor in the absence of B2 receptor inhibits cell migration in vitro and decreases tumor formation in vivo. Moreover, tumors formed from cells stimulated with B1-specific agonist showed several features of decreased aggressiveness, such as smaller size and infiltration of inflammatory cells within the tumor area, higher levels of pro-inflammatory cytokines implicated in the host anti-tumor immune response, lower number of cells undergoing mitosis, a poorer vascular network, no signs of invasion of surrounding tissues or metastasis and increased animal survival. Our findings reveal that activation of the kinin B1 receptor has a host protective role during murine melanoma tumor progression, suggesting that the B1 receptor could be a new anti-tumor GPCR and provide new opportunities for therapeutic targeting.
    PLoS ONE 05/2013; 8(5):e64453. DOI:10.1371/journal.pone.0064453 · 3.53 Impact Factor
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    ABSTRACT: Renal cell carcinoma (RCC) is characterized by high vascular endothelial growth factor (VEGF) production and, consequently, excessive angiogenesis. Several strategies have been developed to target angiogenesis as a method for treating metastatic RCC (mRCC). Endostatin (ES) is a C-terminal fragment of collagen XVIII that has antiangiogenic activity. The aim of this study was to investigate the predictive value of circulating VEGF-A in a murine model of mRCC after ES gene therapy. ES therapy did not affect the levels of collagen XVIII/ES or ES in the tissue. The circulating level of ES was increased in the control and ES-treated groups (normal vs. control, P<0.05 and ES-treated vs. control, P<0.001), and the intratumoral vessels were significantly decreased (ES-treated vs. control, P<0.05). ES therapy decreased the VEGF mRNA levels. The tissue and circulating levels of VEGF in the control group were significantly higher than normal (P<0.01 and P<0.05, respectively). Treatment with ES significantly reduced the VEGF concentrations in both compartments (P<0.001 for tissue and P<0.05 for plasma). Our findings indicate that in addition to the directly targeted tumor vessels, ES exerts its antitumor effect by down-regulating VEGF gene expression in renal tumor cells. Additionally, our findings point to the predictive value of VEGF for ES therapy.
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 05/2013; DOI:10.1016/j.biopha.2013.04.008 · 2.11 Impact Factor
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    ABSTRACT: Abstract A role for the kinin B1 receptor in energy-homeostatic processes was implicated by previous works. Notably the studies where kinin B1 receptor knockout mice (B1-/-) are observed to have impaired adiposity, impaired leptin and insulin production, lower feed efficiency, protection from liver steatosis and diet induced obesity when fed a high fat diet (HFD). More particularly, in a model where the B1 receptor is expressed exclusively in the adipose tissue, it rescues the plasma insulin concentration and the weight gain seen in wild type mice. Taking into consideration that leptin participates in the formation of hypothalamic nuclei, which modulate energy expenditure, and feeding behavior, we hypothesized that these brain regions could also be altered in B1-/- mice. We observed for the first time a difference in the gene expression pattern of CART (cocaine-and-amphetamine related transcript) in the LHA (lateral hypothalamic area) resulting from the deletion of the kinin B1 receptor gene. The correlation between CART expression in the LHA and the thwarting of diet-induced obesity corroborates independent correlations between CART and obesity. Further it seems to indicate that the mechanism underlying the 'lean' phenotype of B1-/- mice is not solely stemming from changes in peripheral tissues but may also receive contributions from changes in the hypothalamic machinery involved in energy homeostasis processes.
    Biological Chemistry 03/2013; DOI:10.1515/hsz-2012-0302 · 2.69 Impact Factor
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    ABSTRACT: Fabry disease (FD) is an X-linked inborn error of glycosphingolipid catabolism that results from mutations in the alpha-galactosidase A (GLA) gene. Evaluating the enzymatic activity in male individuals usually performs the diagnosis of the disease, but in female carriers the diagnosis should be based on DNA sequencing (DS), since enzyme assays is often inconclusive due to inactivation of chromosome X. This work presents genotyping of GLA gene in 568 individuals from 102 families with suspect of FD. In addition, we developed a simple and noninvasive diagnosis by sequencing the messenger RNA (mRNA). In parallel, we correlated the expression of GLA gene by real time PCR. Furthermore, this protocol using RNA extracted from leukocytes avoids the use of biopsies, decreases the amount of fragments to be sequenced, and should open up new perspectives for a more accurate diagnosis and early treatment of Fabry disease.
    Molecular Genetics and Metabolism 02/2013; 108(2):S93. DOI:10.1016/j.ymgme.2012.11.254 · 2.83 Impact Factor
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    ABSTRACT: Multiple sclerosis (MS) is a progressive, demyelinating inflammatory disease of the human central nervous system (CNS). While the primary symptoms of MS affect motor function, it is now recognized that chronic pain is a relevant symptom that affects both animals and MS patients. There is evidence that glial cells, such as astrocytes, play an important role in the development and maintenance of chronic pain. Kinins, notably bradykinin (BK) acting through B1 (B1R) and B2 (B2R) receptors, play a central role in pain and inflammatory processes. However, it remains unclear whether kinin receptors are involved in neuropathic pain in MS. Here we investigated by genetic and pharmacological approaches the role of kinin receptors in neuropathic pain behaviors induced in the experimental autoimmune encephalomyelitis (EAE) mouse model. Our results showed that gene deletion or antagonism of kinin receptors, especially B1R, significantly inhibited both tactile and thermal hypersensitivity in EAE animals. By contrast, animals with EAE and treated with a B1R selective agonist displayed a significant increase in tactile hypersensitivity. We also observed a marked increase in B1R mRNA and protein level in the mouse spinal cord 14 days after EAE immunization. Blockade of B1R significantly suppressed the levels of mRNAs for IL-17, IFN-γ, IL-6, CXCL-1/KC, COX-2 and NOS2, as well as glial activation in the spinal cord. Of note, the selective B1 antagonist DALBK consistently prevented IFN-induced up-regulation of TNF-α and IL-6 release in astrocytes culture. Finally, both B1R and B2R antagonists significantly inhibited COX-2 and NOS2 expression in primary astrocytes culture. The B1R was co-localized with immunomarker of astrocytes in the spinal cord of EAE-treated animals. The above data constitute convincing experimental evidence indicating that both kinin receptors, especially the B1 subtype, exert a critical role in the establishment of persistent hypersensitivity observed in the EAE model, an action that seems to involve a central inflammatory process, possibly acting on astrocytes. Thus, B1 selective antagonists or drugs that reduce kinin release may have the potential to treat neuropathic pain in patients suffering from MS.
    Neurobiology of Disease 02/2013; 54. DOI:10.1016/j.nbd.2013.02.007 · 5.20 Impact Factor
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    ABSTRACT: AIM: The pathophysiology of periodontal diseases involves aspects of immunity and bone remodelling. Considering the role of the kinin B1 receptor (Bdkrb1) in inflammation and healing, the purpose of this study was to evaluate the contribution of Bdkrb1 to the pathogenesis of periodontitis. MATERIAL AND METHODS: We used a model of ligature-induced experimental periodontitis (LIEP) in mice lacking Bdkrb1 (Bdkrb1(-/-) ) to test the role of this receptor in bone loss and cytokine secretion by lymph nodes cells. Angiotensin-converting enzyme inhibitor (ACEi) was used as a pharmacological strategy to support the genetic model. Also, autonomous effect of Bdkrb1 deletion was evaluated in osteoclasts precursors from bone marrow. RESULTS: Bdkrb1(-/-) mice exhibit increased bone loss and IL-17 secretion in response to LIEP when compared to wild type. LIEP does not modify TNF-α, IFN-γ and IL-10 levels in Bdkrb1(-/-) mice after 21 days. Bone marrow cells from Bdkrb1(-/-) displayed increased differentiation into functional osteoclasts with consistent artificial calcium phosphate degradation. Furthermore, treatment of mice with ACEi prevented bone destruction. CONCLUSION: Bdkrb1 participates in the pathogenesis of LIEP bone loss possibly through mechanisms that involve modulation of the TH 17 response, thereby demonstrating its role in the development of periodontitis.
    Journal Of Clinical Periodontology 02/2013; DOI:10.1111/jcpe.12097 · 3.61 Impact Factor

Publication Stats

4k Citations
855.51 Total Impact Points


  • 1998–2015
    • Universidade Federal de São Paulo
      • Departamento de Biofísica
      San Paulo, São Paulo, Brazil
    • French Institute of Health and Medical Research
      • Institute of Metabolic and Cardiovascular Diseases I2MC
      Lutetia Parisorum, Île-de-France, France
  • 2012–2013
    • University of São Paulo
      • Ribeirão Preto School of Medicine (FMRP)
      São Paulo, Estado de Sao Paulo, Brazil
  • 1996–2007
    • CEP America
      Емеривил, California, United States
  • 2006
    • University of Toronto
      Toronto, Ontario, Canada
    • Universidade de Mogi das Cruzes
      Moji das Cruzes, São Paulo, Brazil
  • 2004–2005
    • Federal University of Santa Catarina
      • Centro de Ciências Biológicas (CCB)
      Florianópolis, Estado de Santa Catarina, Brazil
  • 1999–2002
    • Max-Delbrück-Centrum für Molekulare Medizin
      Berlín, Berlin, Germany
    • Institut Louis Bachelier
      Lutetia Parisorum, Île-de-France, France
  • 1992–2002
    • Federal University of Minas Gerais
      • Instituto de Cîências Biológicas (ICB)
      Belo Horizonte, Estado de Minas Gerais, Brazil
  • 2000
    • Freie Universität Berlin
      • Division of Biochemistry
      Berlín, Berlin, Germany