CARLOS ALBERTO MOREIRA FILHO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Pediatria, Faculdade de Medicina - Docente
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina - Líder
15 resultados
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conferenceObject TRISOMY 21-DRIVEN GENE EXPRESSION DYSREGULATION IN HUMAN THYMUS: CONVERGING GENOMIC AND EPIGENOMIC MECHANISMS(2016) MOREIRA-FILHO, Carlos Alberto; BANDO, Silvia Yumi; BERTONHA, Fernanda Bernardi; SILVA, Filipi Nascimento; COSTA, Luciano da Fontoura; FEREIRA, Leandro Rodrigues; CARNEIRO-SAMPAIO, MagdaconferenceObject Sexual Dimorphism and AIRE-AIRE Interactors-miRNA Coexpression Networks in the Infant Human Thymus(2019) BANDO, Silvia Y.; BERTONHA, Fernanda B.; OLIVEIRA, Lucila H. B.; MOREIRA-FILHO, Carlos Alberto; CARNEIRO-SAMPAIO, MagdaconferenceObject Complete Transcriptional Network Driven-View of Thymic Hypofunction in Down Syndrome(2014) MOREIRA-FILHO, Carlos Alberto; BANDO, Silvia Yumi; BERTONHA, Fernanda Bernardi; FEREIRA, Leandro Rodrigues; SILVA, Filipi Nascimento; COSTA, Luciano da Fontoura; GRASSI, Marcilia Sierro; CARNEIRO-SAMPAIO, Magda- Early infiltration of p40IL12(+)CCR7(+)CD11b(+) cells is critical for fibrosis development(2016) BRAGA, Tarcio Teodoro; CORREA-COSTA, Matheus; AZEVEDO, Hatylas; SILVA, Reinaldo Correia; CRUZ, Mario Costa; ALMEIDA, Maira Estanislau Soares; HIYANE, Meire Ioshie; MOREIRA-FILHO, Carlos Alberto; SANTOS, Marinilce Fagundes; PEREZ, Katia Regina; CUCCOVIA, Iolanda Midea; CAMARA, Niels Olsen SaraivaIntroductionMacrophages are heterogeneous and thus can be correlated with distinct tissue outcomes after injury. Conflicting data have indicated that the M2-related phenotype directly triggers fibrosis. Conversely, we hypothesize here that the inflammatory milieu provided by early infiltration of pro-inflammatory macrophages dictates tissue scarring after injury. Methods and ResultsWe first determined that tissue-localized macrophages exhibit a pro-inflammatory phenotype (p40IL12(+)CCR7(+)CD11b(+)) during the early phase of a chronic injury model, in contrast to a pro-resolving phenotype (Arg1(+)IL10(+)CD206(+)CD11b(+)) at a later stage. Then, we evaluated the effects of injecting macrophages differentiated in vitro in the presence of IFN+LPS or IL4+IL13 or non-differentiated macrophages (hereafter, M0) on promoting inflammation and progression of chronic injury in macrophage-depleted mice. In addition to enhancing the expression of pro-inflammatory cytokines, the injection of M (IFN+LPS), but not M (IL4+IL13) or M0, accentuated fibrosis while augmenting levels of anti-inflammatory molecules, increasing collagen deposition and impairing organ function. We observed a similar profile after injection of sorted CCR7(+)CD11b(+) cells and a more pronounced effect of M (IFN+LPS) cells originated from Stat6(-/-) mice. The injection of M (IFN+LPS) cells was associated with the up-regulation of inflammation- and fibrosis-related proteins (Thbs1, Mmp7, Mmp8, and Mmp13). ConclusionsOur results suggest that pro-inflammatory macrophages promote microenvironmental changes that may lead to fibrogenesis by inducing an inflammatory milieu that alters a network of extracellular-related genes, culminating in tissue fibrosis.
conferenceObject MODULAR TRANSCRIPTIONAL REPERTOIRE AND microRNA-TARGET ANALYSES IN THYMIC TISSUE OF DOWN SYNDROME INFANTS(2015) MOREIRA-FILHO, Carlos Alberto; BANDO, Silvia Yumi; BERTONHA, Fernanda Bernardi; SILVA, Filipi Nascimento; COSTA, Luciano da Fontoura; FEREIRA, Leandro Rodrigues; CARNEIRO-SAMPAIO, Magdaarticle 14 Citação(ões) na Scopus Effects of acute aerobic exercise on leukocyte inflammatory gene expression in systemic lupus erythematosus(2016) PERANDINI, L. A.; SALES-DE-OLIVEIRA, D.; ALMEIDA, D. C.; AZEVEDO, H.; MOREIRA-FILHO, C. A.; CENEDEZE, M. A.; BENATTI, F. B.; LIMA, F. R.; BORBA, E.; BONFA, E.; SA-PINTO, A. L.; ROSCHEL, H.; CAMARA, N. O.; GUALANO, B.Systemic lupus erythematosus (SLE) is an autoimmune disease with a persistent systemic inflammation. Exercise-induced inflammatory response in SLE remains to be fully elucidated. The aim of this study was to assess the effects of acute exercise on leukocyte gene expression in active (SLEACTIVE) and inactive SLE (SLEINACTIVE) patients and healthy controls (HC). Methods: All subjects (n = 4 per group) performed a 30-min single bout of acute aerobic exercise (similar to 70% of VO2 peak) on a treadmill, and blood samples were collected for RNA extraction from circulating leukocyte at baseline, at the end of exercise, and after three hours of recovery. The expression of a panel of immune-related genes was evaluated by a quantitative PCR array assay. Moreover, network-based analyses were performed to interpret transcriptional changes occurring after the exercise challenge. Results: In all groups, a single bout of acute exercise led to the down-regulation of the gene expression of innate and adaptive immunity at the end of exercise (e.g., TLR3, IFNG, GATA3, FOXP3, STAT4) with a subsequent up-regulation occurring upon recovery. Exercise regulated the expression of inflammatory genes in the blood leukocytes of the SLE patients and HC, although the SLE groups exhibited fewer modulated genes and less densely connected networks (number of nodes: 29, 40 and 58; number of edges: 29, 60 and 195; network density: 0.07, 0.08 and 0.12, for SLEACTIVE, SLEINACTIVE and HC, respectively). Conclusion: The leukocytes from the SLE patients, irrespective of disease activity, showed a down-regulated inflammatory gene expression immediately after acute aerobic exercise, followed by an up-regulation at recovery. Furthermore, less organized gene networks were observed in the SLE patients, suggesting that they may be deficient in triggering a normal exercise-induced immune transcriptional response.- A Regulatory miRNA-mRNA Network Is Associated with Tissue Repair Induced by Mesenchymal Stromal Cells in Acute Kidney Injury(2017) ALMEIDA, Danilo Candido de; BASSI, Enio Jose; AZEVEDO, Hatylas; ANDERSON, Leticia; ORIGASSA, Clarice Silvia Taemi; CENEDEZE, Marcos Antonio; ANDRADE-OLIVEIRA, Vinicius de; FELIZARDO, Raphael Jose Ferreira; SILVA, Reinaldo Correia da; HIYANE, Meire Ioshie; SEMEDO, Patricia; REIS, Marlene Antonia dos; MOREIRA-FILHO, Carlos Alberto; VERJOVSKI-ALMEIDA, Sergio; PACHECO-SILVA, Alvaro; CAMARA, Niels Olsen SaraivaMesenchymal stromal cells (MSCs) orchestrate tissue repair by releasing cell-derived microvesicles (MVs), which, presumably by small RNA species, modulate global gene expression. The knowledge of miRNA/mRNA signatures linked to a reparative status may elucidate some of the molecular events associated with MSC protection. Here, we used a model of cisplatin-induced kidney injury (acute kidney injury) to assess how MSCs or MVs could restore tissue function. MSCs and MVs presented similar protective effects, which were evidenced in vivo and in vitro by modulating apoptosis, inflammation, oxidative stress, and a set of prosurvival molecules. In addition, we observed that miRNAs (i.e., miR-880, miR-141, miR-377, and miR-21) were modulated, thereby showing active participation on regenerative process. Subsequently, we identified that MSC regulates a particular miRNA subset which mRNA targets are associated with Wnt/TGF-beta fibrosis, and epithelial-mesenchymal transition signaling pathways. Our results suggest that MSCs release MVs that transcriptionally reprogram injured cells, thereby modulating a specific miRNA-mRNA network.
- Decreased AIRE Expression and Global Thymic Hypofunction in Down Syndrome(2011) LIMA, Flavia A.; MOREIRA-FILHO, Carlos A.; RAMOS, Patricia L.; BRENTANI, Helena; LIMA, Leandro de A.; ARRAIS, Magaly; BENTO-DE-SOUZA, Luiz C.; BENTO-DE-SOUZA, Luciana; DUARTE, Maria I.; COUTINHO, Antonio; CARNEIRO-SAMPAIO, MagdaThe Down syndrome (DS) immune phenotype is characterized by thymus hypotrophy, higher propensity to organ-specific autoimmune disorders, and higher susceptibility to infections, among other features. Considering that AIRE (autoimmune regulator) is located on 21q22.3, we analyzed protein and gene expression in surgically removed thymuses from 14 DS patients with congenital heart defects, who were compared with 42 age-matched controls with heart anomaly as an isolated malformation. Immunohistochemistry revealed 70.48 +/- 49.59 AIRE-positive cells/mm(2) in DS versus 154.70 +/- 61.16 AIRE-positive cells/mm(2) in controls (p < 0.0001), and quantitative PCR as well as DNA microarray data confirmed those results. The number of FOXP3-positive cells/mm(2) was equivalent in both groups. Thymus transcriptome analysis showed 407 genes significantly hypoexpressed in DS, most of which were related, according to network transcriptional analysis (FunNet), to cell division and to immunity. Immune response-related genes included those involved in 1) Ag processing and presentation (HLA-DQB1, HLA-DRB3, CD1A, CD1B, CD1C, ERAP) and 2) thymic T cell differentiation (IL2RG, RAG2, CD3D, CD3E, PRDX2, CDK6) and selection (SH2D1A, CD74). It is noteworthy that relevant AIRE-partner genes, such as TOP2A, LAMNB1, and NUP93, were found hypoexpressed in DNA microarrays and quantitative real-time PCR analyses. These findings on global thymic hypofunction in DS revealed molecular mechanisms underlying DS immune phenotype and strongly suggest that DS immune abnormalities are present since early development, rather than being a consequence of precocious aging, as widely hypothesized. Thus, DS should be considered as a non-monogenic primary immunodeficiency. The Journal of Immunology, 2011, 187: 3422-3430.
conferenceObject Congenital hypothyroidism associated with IPEX Congenital hypothyroidism associated with IPEX Congenital hypothyroidism associated with IPEX Congenital hypothyroidism and IPEX(2022) LIMA, Susana; NUNCIO, Fabio De; BARROS-CAMPOS, Nathalia; MOREIRA-FILHO, Carlos; CARNEIRO-SAMPAIO, Magda- Prevalence of Inflammatory Pathways Over Immuno-Tolerance in Peripheral Blood Mononuclear Cells of Recent-Onset Type 1 Diabetes(2022) SANTOS, Aritania Sousa; CUNHA-NETO, Edecio; GONFINETTI, Nelson Vinicius; BERTONHA, Fernanda Bernardi; BROCHET, Pauline; BERGON, Aurelie; MOREIRA-FILHO, Carlos Alberto; CHEVILLARD, Christophe; SILVA, Maria Elizabeth Rossi daBackgroundChanges in innate and adaptive immunity occurring in/around pancreatic islets had been observed in peripheral blood mononuclear cells (PBMC) of Caucasian T1D patients by some, but not all researchers. The aim of our study was to investigate whether gene expression patterns of PBMC of the highly admixed Brazilian population could add knowledge about T1D pathogenic mechanisms. MethodsWe assessed global gene expression in PBMC from two groups matched for age, sex and BMI: 20 patients with recent-onset T1D (<= 6 months from diagnosis, in a time when the autoimmune process is still highly active), testing positive for one or more islet autoantibodies and 20 islet autoantibody-negative healthy controls. ResultsWe identified 474 differentially expressed genes between groups. The most expressed genes in T1D group favored host defense, inflammatory and anti-bacterial/antiviral effects (LFT, DEFA4, DEFA1, CTSG, KCNMA1) and cell cycle progression. Several of the downregulated genes in T1D target cellular repair, control of inflammation and immune tolerance. They were related to T helper 2 pathway, induction of FOXP3 expression (AREG) and immune tolerance (SMAD6). SMAD6 expression correlated negatively with islet ZnT8 antibody. The expression of PDE12, that offers resistance to viral pathogens was decreased and negatively related to ZnT8A and GADA levels. The increased expression of long non coding RNAs MALAT1 and NEAT1, related to inflammatory mediators, autoimmune diseases and innate immune response against viral infections reinforced these data ConclusionsOur analysis suggested the activation of cell development, anti-infectious and inflammatory pathways, indicating immune activation, whereas immune-regulatory pathways were downregulated in PBMC from recent-onset T1D patients with a differential genetic profile.