WALCY PAGANELLI ROSOLIA TEODORO

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Lattes
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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

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Autor: CAPELOZZI, Vera Luiza ×

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  • conferenceObject
    Collagen V activation and matrix extracellular remodeling mediated pulmonary fibrosis in experimental models of bleomycin and 3-5-di-tert-4-hidroxitoluene
    (2013) LOPES, Deborah; MARTINS, Vanessa; TEODORO, Walcy; ROGER, Edwin; CAPELOZZI, Vera Luiza
  • article 8 Citação(ões) na Scopus
    Early type I collagen deposition is associated with prognosis in biliary atresia
    (2016) LONGO-SANTOS, Luis Ricardo; TEODORO, Walcy Rosolia; MELLO, Evandro Sobroza de; VELOSA, Ana Paula Pereira; PARRA, Edwin Roger; CAPELOZZI, Vera Luiza; TANNURI, Uenis
    Background: Biliary atresia (BA) is a cholestatic liver disease of children that progresses to hepatic fibrosis. BA is the main indication of pediatric liver transplantation (LTx). Histopathological markers in liver biopsies could be useful for predicting progression to end-stage disease. Objective: To establish histopathological or immunohistochemical markers in liver biopsies of BA patients and correlate those markers with prognosis. Method: Histological analysis of biliary alterations and morphometric assessment of liver fibrosis were performed, in addition to indirect immunofluorescence assays (IF) for type I, III, IV and V collagens in initial and final liver biopsies of 36 patients with BA who underwent Kasai hepatoportoenterostomy (KPE) and LTx in the last 20 years at a single center. Results: Histopathologicalmarkers had no correlation with evolutive time until LTx. The perisinusoidal deposition of type III and V collagens was more prominent in the initial biopsies (p < 0.01), whereas deposition of type I and IV collagens indicated progression (p < 0.01). Patients with large amounts of perisinusoidal type I collagen in the initial biopsies had worse progression time curves until LTx (p = 0.04). Conclusion: Morphometric assessment of perisinusoidal deposition of type I collagen by IF in the initial biopsy can correlate with progression time to LTx in post-surgical BA.
  • article 4 Citação(ões) na Scopus
    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 Luiza
    Anomalous 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.
  • article 1 Citação(ões) na Scopus
    Sterilized human skin graft with a dose of 25 kGy provides a privileged immune and collagen microenvironment in the adhesion of Nude mice wounds
    (2022) MIRANDA, Jurandir Tomaz de; BRINGEL, Fabiana de Andrade; VELOSA, Ana Paula Pereira; PROTOCEVICH, Veronica; FERNEZLIAN, Sandra de Morais; SILVA, Pedro Leme; CAPELOZZI, Vera Luiza; MATHOR, Monica Beatriz; TEODORO, Walcy Rosolia
    This study aimed to report the effects of different doses of ionizing radiation on inflammatory and repair stage of human skin graft adherence in Nude mice wounds. Animals were divided into transplanted with irradiated human skin grafts (IHSG) at 25 and 50 kGy (IHSG 25 kGy; IHSG 50 kGy) and non-IHSG and euthanized on the 3rd, 7th and 21st days after the surgery, by gross and microscopic changes, immunostaining for human type I collagen (Col I) and mouse Col I and Col III and inflammatory cells. We found an effectiveness of human split-thickness graft adherence in mice transplanted with IHSG 25 kGy, as well decrease in dermo-epidermal necrosis and neutrophils, lower loss of skin thickness, epithelization and neo-vascularization. Day 21 post-transplantation with IHSG 25 kGy was observed a well-preserved human skin in the border of the graft, a prominent granulation tissue in an organization by proliferated fibroblasts, Col III deposition and increased B-cells and macrophages. A complete adherence of human skin graft occurred with IHSG 25 kGy. We suggest that the ionizing radiation at 25 kGy mediates inflammation and the repair stage of human skin graft adherence in murine model, thus emerging as a potential tool in healing cutaneous wounds.
  • conferenceObject
    Pulmonary fibrosis modulation by mesenchymal stem cells and conditioned medium
    (2019) FELIX, Renato Goncalves; BOVOLATO, Ana Livia Carvalho Bovolato Carvalho; LEAO, Patricia Dos Santos Leao Dos Santos; GOLIM, Marjorie De Assis Golim De Assis; TEODORO, Walcy Rosolia Teodoro Rosolia; FABRO, Alexandre Todorovic; DEFFUNE, Elenice; CAPELOZZI, Vera Luiza
  • article 7 Citação(ões) na Scopus
    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 Luiza
    This 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.
  • article 3 Citação(ões) na Scopus
    Effects of different fluid management on lung and kidney during pressure-controlled and pressure-support ventilation in experimental acute lung injury
    (2022) CARVALHO, Eduardo Butturini de; FONSECA, Ana Carolina Fernandes; MAGALHAES, Raquel Ferreira; PINTO, Eliete Ferreira; SAMARY, Cynthia dos Santos; ANTUNES, Mariana Alves; BALDAVIRA, Camila Machado; SILVEIRA, Lizandre Keren Ramos da; TEODORO, Walcy Rosolia; ABREU, Marcelo Gama de; CAPELOZZI, Vera Luiza; FELIX, Nathane Santanna; PELOSI, Paolo; ROCCO, Patricia Rieken Macedo; SILVA, Pedro Leme
    Optimal fluid management is critical during mechanical ventilation to mitigate lung damage. Under normovolemia and protective ventilation, pulmonary tensile stress during pressure-support ventilation (PSV) results in comparable lung protection to compressive stress during pressure-controlled ventilation (PCV) in experimental acute lung injury (ALI). It is not yet known whether tensile stress can lead to comparable protection to compressive stress in ALI under a liberal fluid strategy (LF). A conservative fluid strategy (CF) was compared with LF during PSV and PCV on lungs and kidneys in an established model of ALI. Twenty-eight male Wistar rats received endotoxin intratracheally. After 24 h, they were treated with CF (minimum volume of Ringer's lactate to maintain normovolemia and mean arterial pressure >= 70 mmHg) or LF (similar to 4 times higher than CF) combined with PSV or PCV (VT = 6 ml/kg, PEEP = 3 cmH(2)O) for 1 h. Nonventilated animals (n = 4) were used for molecular biology analyses. CF-PSV compared with LF-PSV: (1) decreased the diffuse alveolar damage score (10 [7.8-12] vs. 25 [23-31.5], p = 0.006), mainly due to edema in axial and alveolar parenchyma; (2) increased birefringence for occludin and claudin-4 in lung tissue and expression of zonula-occludens-1 and metalloproteinase-9 in lung. LF compared with CF reduced neutrophil gelatinase-associated lipocalin and interleukin-6 expression in the kidneys in PSV and PCV. In conclusion, CF compared with LF combined with PSV yielded less lung epithelial cell damage in the current model of ALI. However, LF compared with CF resulted in less kidney injury markers, regardless of the ventilatory strategy.
  • article 3 Citação(ões) na Scopus
    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 Rosolia
    Because 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.
  • article 16 Citação(ões) na Scopus
    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 Luiza
    Posterior 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.
  • article 2 Citação(ões) na Scopus
    In situ evidence of collagen V and signaling pathway of found inflammatory zone 1 (FIZZ1) is associated with silicotic granuloma in lung mice
    (2020) MARTINS, Vanessa; SILVA, Adriana Lopes da; TEODORO, Walcy Rosolia; VELOSA, Ana Paula Pereira; BALANCIN, Marcelo Luiz; CRUZ, Fernanda Ferreira; SILVA, Pedro Leme; ROCCO, Patricia Rieken Macedo; CAPELOZZI, Vera Luiza
    Inhalation of silica particles causes silicosis: an occupational lung disease characterized by persistent inflammation with granuloma formation that leads to tissue remodeling and impairment of lung function. Although silicosis has been studied intensely, little is known about the crucial cellular mechanisms that initiate and drive the process of inflammation and fibrosis. Recently, found in inflammatory zone 1 (FIZZ1) protein, produced by alveolar macrophages and fibroblasts have been shown to induce the proliferation of myofibroblasts and their transdifferentiation, causing tissue fibrosis. Moreover, autoimmunogenic collagen V, produced by alveolar epithelial cells and fibroblasts, is involved in the pathophysiology of interstitial pulmonary fibrosis and bleomycin-induced lung fibrosis. Based on the aforementioned we hypothesized that FIZZ1 and collagen V may be involved in the silicotic granuloma process in mice lungs. Male C57BL/6 mice (N = 20) received intratracheal administration of silica particles (Silica; 20 mg in 50 mu L saline) or saline (Control; 50 mu L). After 15 days, the lung histology was performed through immunohistochemistry and morphometric analysis. Within silicotic granulomas, collagen V and FIZZ1 increased, while peroxisome proliferator-activated receptor gamma (PPAR gamma) positive cells decreased. In addition, the expression of proteins Notch-1, alpha smooth muscle actin (alpha-SMA) and macrophages163 (CD163) were higher in silicotic granulomas than control lungs. A significant positive correlation was found between collagen V and FIZZ1 (r = 0.70; p < 0.05), collagen V and Notch-1 (r = 0.72; p < 0.05), whereas Collagen V was inversely associated with peroxisome proliferator-activated receptor gamma (r=-0.69; p < 0.05). These findings suggested that collagen V association with FIZZ1, Notch-1 and PPAR gamma might be a key pathogenic mechanism for silicotic granulomas in mice lungs.