WALCY PAGANELLI ROSOLIA TEODORO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina
LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina
LIM/02 - Laboratório de Anatomia Médico-Cirúrgica, Hospital das Clínicas, Faculdade de Medicina
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina
LIM/02 - Laboratório de Anatomia Médico-Cirúrgica, Hospital das Clínicas, Faculdade de Medicina
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina
8 resultados
Resultados de Busca
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conferenceObject Pathophysiological features of lung and skin in human SSc and collagen V/C57LB6 mouse model(2018) TEODORO, W. Paganelli Rosolia; VELOSA, A. P. Pereira; QUEIROZ, Z. A. de Jesus; SANTOS, L. Araujo dos; CATANOZI, S.; SANTOS FILHO, A. dos; BUENO, C.; VENDRAMINI, M. Borges Galhardo; FERNEZLIAN, S. de Moraes; EHER, E. Miristene; LOPES, F. Degobbi T. Q. S.; CAPELOZZI, V. L.- Butylated hydroxytoluene induces type-V collagen and overexpression of remodeling genes/proteins in experimental lung fibrosis(2018) MARTINS, Vanessa; TEODORO, Walcy Rosolia; VELOSA, Ana Paula Pereira; ANDRADE, Priscila; FARHAT, Cecilia; FABRO, Alexandre Todorovic; CAPELOZZI, Vera LuizaAnomalous histoarchitecture with increased levels of type-V collagen (Col V) in lungs of human idiopathic pulmonary fibrosis (IPF) and bleomycin (BLM) airway-centered interstitial fibrosis suggest that this collagen can be a possible trigger involved in the pathogenesis of these diseases. Butylated hydroxytoluene (BHT) injury model revealed a distal involvement of lung parenchyma with significant endothelial injury and fibrotic response, contrasting with the BLM airway-centered insult. We undertook this study to analyze whether BHT alters distal airway/alveolar epithelial cells (AECs) and extracellular matrix (ECM) signaling involved in the initiation and progression of pulmonary fibrosis in a different pathway concerning overexpression of Col V. Female mice C57BL/6 (n=6) were instilled intraperitoneally with 400mg/kg of BHT dissolved in 1 mL of corn oil and euthanized at day 14 or 21 after BHT administration. Morphometry, immunohistochemistry and transmission electron microscopy were performed to characterize microscopic and submicroscopic changes of AECs and endothelial cells through transforming growth factor beta (TGF-beta) basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) expression. Immunofluorescence and immunogold electron microscopy were performed to characterize Col V. Quantitative polymerase chain reaction (qPCR) was used to confirm differential levels of RNA messenger. BHT lungs showed marked fibrotic areas and hyperplastic AECs. The alveolar damage caused destruction of elastic fibers and a critical increase of Col V in ECM of distal lung parenchyma. Fibrogenesis-promoting markers TGF-beta, bFGF and VEGF were also overexpressed in situ, coinciding with up-regulation in remodeling enzymes, growth factors, cytokines, transduction and transcription genes. BHT alters distal lung parenchyma signaling involved in pulmonary fibrosis highlighted similarities to human IPF in a pathway involving Col V arising as a promissory model to identify effective therapeutic targets.
- Comprehensive analysis of immune, extracellular matrices and pathogens profile in lung granulomatosis of unexplained etiology(2018) SOUZA, Paola da Costa; DONDO, Patricia Suemi; SOUZA, Gabriela; LOPES, Deborah; MOSCARDI, Marcel; MARTINHO, Vinicius de Miranda; LOURENCO, Rodolfo Daniel de Mattos; PRIETO, Tabatha; BALANCIN, Marcelo Luiz; ASSATO, Aline Kawassaki; TEODORO, Walcy Rosolia; RODRIGUES, Silvia; LIMA, Mariana; CASTELLANO, Maria Vera; COLETTA, Ester; PARRA, Edwin Roger; CAPELOZZI, Vera LuizaThis study analyzed the type 1 and type 2 T helper (Th1/Th2) cytokines (including interleukins), immune cellular, matrix profile, and pathogens in granulomas with unexplained etiology compared to those with infectious and noninfectious etiology. Surgical lung biopsies from 108 patients were retrospectively reviewed. Histochemistry, immunohistochemistry, immunofluorescence, morphometry and polymerase chain reaction were used, respectively, to evaluate total collagen and elastin fibers, collagen I and III, immune cells, cytokines, matrix metalloproteinase-9, myofibroblasts, and multiple usual and unusual pathogens. No relevant polymerase chain reaction expression was found in unexplained granulomas. A significant difference was found between the absolute number of eosinophils, macrophages, and lymphocytes within granulomas compared to uninvolved lung tissue. Granulomas with unexplained etiology (UEG) presented increased number of eosinophils and high expression of interleukins (ILs) IL-4/IL-5 and transforming growth factor-beta. In sarcoidosis, CD4/CD8 cell number was significantly higher within and outside granulomas, respectively; the opposite was detected in hypersensitivity pneumonitis. Again, a significant difference was found between the high number of myofibroblasts and matrix metalloproteinase-9 in UEG, hypersensitivity pneumonitis, and sarcoidosis compared to granulomas of tuberculosis. Granulomas of paracoccidioisis exhibited increased type I collagen and elastic fibers. Th1 immune cellular profile was similar among granulomas with unexplained, infectious, and noninfectious etiology. In contrast, modulation of Th2 and matrix remodeling was associated with more fibroelastogenesis and scarring of lung tissue in UEG compared to infectious and noninfectious. We concluded that IL-4/IL-5 and transforming growth factor-beta might be used as surrogate markers of early fibrosis, reducing the need for genotyping, and promise therapeutic target in unexplained granulomas.
- Collagen V oral administration decreases inflammation and remodeling of synovial membrane in experimental arthritis(2018) ATAYDE, Silvana Ramos; VELOSA, Ana Paula Pereira; CATANOZI, Sergio; BIANCO, Vanessa Del; ANDRADE, Priscila Cristina; RODRIGUES, Jose Eduardo de Castro M.; SANTOS FILHO, Antonio dos; ANTONANGELO, Leila; MELLO, Suzana Beatriz Verissimo de; CAPELOZZI, Vera Luiza; TEODORO, Walcy RosoliaBecause collagen type V (Col V) can be exposed in tissue injury, we hypothesized that oral administration of this collagen species modulates the inflammation and remodeling of experimental synovitis, avoiding joint destruction, and that the modulation may differ according to the temporal administration. Arthritis (IA, n = 20) was induced in Lewis rats by intraarticular (ia) injection of 500 mu g of methylated bovine serum albumin (mBSA) emulsified in complete Freund's adjuvant (CFA) (10 mu l) followed by an intraarticular booster of mBSA (50 mu g) in saline (50 mu l) administered at 7 and 14 days. The control group received saline (50 mu l, ia). After the first intraarticular injection, ten IA animals were supplemented via gavage with Col V (500 mu g/300 mu l) daily for 30 days (IA/Suppl). The control group received saline (50 mu L) and Col V supplement in the same way (Suppl). Col V oral administration in IA/Suppl led to 1) inhibited edema and severe inflammatory cell infiltration, 2) decreased collagen fiber content, 3) decreased collagen type I, 4) inhibited lymphocyte subpopulations and macrophages, 5) inhibited IL-1 beta, IL-10, IL-17 and TNF-alpha production and 6) increased expression of caspase-9 in the synovial tissue. In conclusion, Col V supplementation decreased synovial inflammation and the fibrotic response, possibly by increased the apoptosis of inflammatory cells.
conferenceObject COLLAGEN V/C57BL6 MOUSE MODEL: A NOVEL PRECLINICAL MODEL TO STUDY PATHOPHYSIOLOGY AND THERAPEUTIC APPROACHES IN SYSTEMIC SCLEROSIS(2018) TEODORO, W. R.; VELOSA, A. P. P.; QUEIROZ, Z. A. de J.; SANTOS, L. A. dos; CATANOZI, S.; SANTOS FILHO, A. dos; BUENO, C.; VENDRAMINI, M.; FERNEZLIAN, S. M.; EHER, E. M.; LOPES, F. D. T. Q. S.; SAMPAIO-BARROS, P. D.; CAPELOZZI, V. L.- Matrix metalloproteinase-1 (MMP-1) and (MMP-8) gene polymorphisms promote increase and remodeling of the collagen III and V in posterior tibial tendinopathy(2018) DINIZ-FERNANDES, Tulio; GODOY-SANTOS, Alexandre Leme; SANTOS, Maria Cristina; PONTIN, Pedro; PEREIRA, Caio Augusto Alves; JARDIM, Yuri Justi; VELOSA, Ana Paula Pereira; MAFFULLI, Nicola; TEODORO, Walcy Rosolia; CAPELOZZI, Vera LuizaPosterior tibial tendinopathy (PTT) can lead to acquired flatfoot in adults. Many patients develop PTT without any identifiable risk factors. Molecular changes in extracellular matrix (ECM) and matrix metalloproteinase (MMP) polymorphism may influence the risk of developing PTT. We aim to investigate the association between matrix metalloproteinase-1 (MMP-1) and (MMP-8) gene polymorphisms with changes in collagen I, III and V in PTT. A case-control study with 22 patients and 5 controls was performed. The MMP-1 (2G/2G) and MMP-8 (T/T) genotypes were determined by PCR-restriction fragment length polymorphism. Tendon specimens were evaluated by a histologic semiquantitative score, immunofluorescence and histomorphometry for collagen I, III and V. Tendon specimens from PTT demonstrated marked distortion of the architecture with necrosis, large basophilic areas with disruption of the normal linear orientation of collagen bundles, infiltration of inflammatory cells, dystrophic calcification and ossification. Under immunofluorescence, PTT tendon specimens showed weak green fluorescence and diffuse distribution of collagen I fibers, but strong fluorescence of collagen III and V. The collagen I fibers were significantly decreased whereas an increase of collagen III and V were found in PTT compared to control groups. In addition, PTT group presented a significant association with MMP-1 and MMP-8 gene polymorphisms. Patients with PTT matrix metalloproteinase-1 (MMP-1) and (MMP-8) gene polymorphisms presented an increase of the collagen III and V ratio, suggesting that the higher proportion in degenerated tendons could contribute to a decrease in the mechanical resistance of the tissue. Still, functional and association studies are needed to elucidate evident roles of MMPs in PTT.
conferenceObject 25 kgy radio-sterilised human skin graft shows effective skin regeneration in nude mice(2018) MIRANDA, J. Tomaz De; BRINGEL, F. De Andrade; PROTOCEVICH, V.; VELOSA, A. P. Pereira; CAPELOZZI, V.; MATHOR, M. B.; TEODORO, W. R.conferenceObject LOW LEVEL LASER THERAPY INCREASES MESENCHYMAL CELL PROLIFERATION AND COLLAGEN II AFTER EXPERIMENTAL INJURY(2018) AKAMATSU, Flavia Emi; TEODORO, Walcy R.; ITEZEROTE, Ana Maria; SALEH, Samir; MARTINEZ, Carlos Augusto Real; RIBEIRO, Marcelo Lima; PEREIRA, Jose Aires; HOJAIJ, Flavio; ANDRADE, Mauro; JACOMO, Alfredo Luiz