BIDOSSESSI WILFRIED HOUNKPE
Projetos de Pesquisa
Unidades Organizacionais
LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
- Transcriptomic characterization of classical monocytes highlights the involvement of immuno-inflammation in bone erosion in Rheumatoid Arthritis(2023) SALES, Lucas Peixoto; HOUNKPE, Bidossessi Wilfried; PEREZ, Mariana Ortega; CAPARBO, Valeria Falco; DOMICIANO, Diogo Souza; BORBA, Eduardo Ferreira; SCHETT, Georg; FIGUEIREDO, Camille Pinto; PEREIRA, Rosa Maria RodriguesIntroduction: Evidence-based data suggest that under inflammatory conditions, classical monocytes are the main source of osteoclasts and might be involved in bone erosion pathophysiology. Here, we analyze the transcriptomic profile of classical monocytes in erosive and non-erosive rheumatoid arthritis patients in order to better understand their contribution to bone erosion.Methods: Thirty-nine premenopausal RA patients were consecutively enrolled and divided into two groups based on the presence of bone erosions on hand joints. Classical monocytes were isolated from peripheral blood through negative selection, and RNA-seq was performed using a poly-A enrichment kit and Illumina (R) platform. Classical monocytes transcriptome from healthy age-matched women were also included to identify differentially expressed genes (DEGs). Therefore, gene sets analysis was performed to identify the enriched biological pathways.Results: RNA-seq analysis resulted in the identification of 1,140 DEGs of which 89 were up-regulated and 1,051 down-regulated in RA patients with bone erosion compared to those without bone erosions. Among up-regulated genes, there was a highlighted expression of IL18RAP and KLF14 related to the production of pro-inflammatory cytokines, innate and adaptive immune response. Genes related to collagen metabolism (LARP6) and bone formation process (PAPPA) were down-regulated in RA patients with erosions. Enriched pathways in patients with erosions were associated with greater activation of immune activation, and inflammation. Interestingly, pathways associated with osteoblast differentiation and regulation of Wnt signaling were less activated in RA patients with erosions.Conclusion: These findings suggest that alterations in expression of monocyte genes related to the inflammatory process and impairment of bone formation might have an important role in the pathophysiology of bone erosions in RA patients.
- RNA-SEQUENCING OF CLASSICAL MONOCYTES FROM RHEUMATOID ARTHRITIS PATIENTS WITH AND WITHOUT BONE EROSION(2023) SALES, L. Peixoto; HOUNKPE, B.; PEREZ, M.; CAPARBO, V.; DOMICIANO, D. S.; BORBA, E.; FIGUEIREDO, C.; PEREIRA, R. M.
- MicroRNA 205-5p and COVID-19 adverse outcomes: Potential molecular biomarker and regulator of the immune response(2023) VAZ, Camila de Oliveira; HOUNKPE, Bidossessi Wilfried; OLIVEIRA, Jose Diogo; MAZETTO, Bruna; JACINTHO, Bruna Cardoso; LOCACHEVIC, Gisele; SOARES, Kaio Henrique De Oliveira; MARIOLANO, Joao Carlos Silva; MESQUITA, Giulia Castilho de; PERES, Karina Colombera; VIEIRA-DAMIANI, Gislaine; GERALDO, Murilo Vieira; ORSI, Fernanda AndradeCoronavirus disease 2019 (COVID-19) is an acute respiratory infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The uncontrolled systemic inflammatory response, resulting from the release of large amounts of pro-inflammatory cytokines, is the main mechanism behind severe acute respiratory syndrome and multiple organ failure, the two main causes of death in COVID-19. Epigenetic mechanisms, such as gene expression regulation by microRNAs (miRs), may be at the basis of the immunological changes associated with COVID-19. Therefore, the main objective of the study was to evaluate whether the expression of miRNAs upon hospital admission could predict the risk of fatal COVID-19. To evaluate the level of circulating miRNAs, we used serum samples of COVID-19 patients collected upon hospital admission. Screening of differentially expressed miRNAs in fatal COVID-19 was performed by miRNA-Seq and the validation of miRNAs by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The Mann-Whitney test and receiver operating characteristic (ROC) curve were used to validate the miRNAs, whose potential signaling pathways and biological processes were identified through an in silico approach. A cohort of 100 COVID-19 patients was included in this study. By comparing the circulating levels of miRs between survivors and patients who died due to complications of the infection, we found that the expression of miR-205-5p was increased in those who died during hospitalization, and the expression of both miR-205-5p (area under the curve [AUC] = 0.62, 95% confidence interval [CI] = 0.5-0.7, P = 0.03) and miR-206 (AUC = 0.62, 95% CI = 0.5-0.7, P = 0.03) was increased in those who lately evolved to severe forms of the disease (AUC = 0.70, 95% CI = 0.6-0.8, P = 0.002).""In silico"" analysis revealed that miR-205-5p has the potential to enhance the activation of NLPR3 inflammasome and to inhibit vascular endothelial growth factor (VEGF) pathways. Impaired innate immune response against SARS-CoV-2 may be explained by epigenetic mechanisms, which could form early biomarkers of adverse outcomes.
- Transcriptomic analysis of elderly women with low muscle mass: association with immune system pathway(2021) NETO, Levi H. Jales; HOUNKPE, Bidossessi W.; FERNANDES, Georgea H.; TAKAYAMA, Liliam; LOPES, Neuza H. M.; PEREIRA, Alexandre C.; PEREIRA, Rosa M. R.Despite the well-established association of gene expression deregulation with low muscle mass (LMM), the associated biological mechanisms remain unclear. Transcriptomic studies are capable to identify key mediators in complex diseases. We aimed to identify relevant mediators and biological mechanisms associated with age-related LMM. LMM-associated genes were detected by logistic regression using microarray data of 20 elderly women with LMM and 20 age and race-matched controls extracted from our SPAH Study (GSE152073). We performed weighted gene co-expression analysis (WGCNA) that correlated the identified gene modules with laboratorial characteristics. Gene enrichment analysis was performed and an LMM predictive model was constructed using Support Vector Machine (SVM). Overall, 821 discriminating transcripts clusters were identified (vertical bar beta coefficient vertical bar 1; p-value <0.01). From this list, 45 predictors of LMM were detected by SVM and validated with 0.7 of accuracy. Our results revealed that the well-described association of inflammation, immunity and metabolic alterations is also relevant at transcriptomic level. WGCNA highlighted a correlation of genes modules involved in immunity pathways with vitamin D level (R = 0.63, p = 0.004) and the Agatston score (R = 0.51, p = 0.02). Our study generated a predicted regulatory network and revealed significant metabolic pathways related to aging processes, showing key mediators that warrant further investigation.
conferenceObject Transcriptome Analysis of Elderly Women with Low Muscle Mass Reveals an Association with Immune System Pathway(2022) HOUNKPE, Bidossessi Wilfried; JALES NETO, Levi Higino; FERNANDES, Georgea H.; TAKAYAMA, Liliam; CAPARBO, Valeria F.; LOPES, Neuza H. M.; PEREIRA, Alexandre C.; PEREIRA, Rosa M. R.- Transcriptomics and network analysis highlight potential pathways in the pathogenesis of pterygium(2022) GUIMARAES, Juliana Albano de; HOUNPKE, Bidossessi Wilfried; DUARTE, Bruna; BOSO, Ana Luiza Mylla; VITURINO, Marina Goncalves Monteiro; BAPTISTA, Leticia de Carvalho; MELO, Monica Barbosa de; ALVES, MonicaPterygium is a common ocular surface condition frequently associated with irritative symptoms. The precise identity of its critical triggers as well as the hierarchical relationship between all the elements involved in the pathogenesis of this disease are not yet elucidated. Meta-analysis of gene expression studies represents a novel strategy capable of identifying key pathogenic mediators and therapeutic targets in complex diseases. Samples from nine patients were collected during surgery after photo documentation and clinical characterization of pterygia. Gene expression experiments were performed using Human Clariom D Assay gene chip. Differential gene expression analysis between active and atrophic pterygia was performed using limma package after adjusting variables by age. In addition, a meta-analysis was performed including recent gene expression studies available at the Gene Expression Omnibus public repository. Two databases including samples from adults with pterygium and controls fulfilled our inclusion criteria. Meta-analysis was performed using the Rank Production algorithm of the RankProd package. Gene set analysis was performed using ClueGO and the transcription factor regulatory network prediction was performed using appropriate bioinformatics tools. Finally, miRNA-mRNA regulatory network was reconstructed using up-regulated genes identified in the gene set analysis from the meta-analysis and their interacting miRNAs from the Brazilian cohort expression data. The meta-analysis identified 154 up-regulated and 58 down-regulated genes. A gene set analysis with the top up-regulated genes evidenced an overrepresentation of pathways associated with remodeling of extracellular matrix. Other pathways represented in the network included formation of cornified envelopes and unsaturated fatty acid metabolic processes. The miRNA-mRNA target prediction network, also reconstructed based on the set of up-regulated genes presented in the gene ontology and biological pathways network, showed that 17 target genes were negatively correlated with their interacting miRNAs from the Brazilian cohort expression data. Once again, the main identified cluster involved extracellular matrix remodeling mechanisms, while the second cluster involved formation of cornified envelope, establishment of skin barrier and unsaturated fatty acid metabolic process. Differential expression comparing active pterygium with atrophic pterygium using data generated from the Brazilian cohort identified differentially expressed genes between the two forms of presentation of this condition. Our results reveal differentially expressed genes not only in pterygium, but also in active pterygium when compared to the atrophic ones. New insights in relation to pterygium's pathophysiology are suggested.