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
7 resultados
Resultados de Busca
Agora exibindo 1 - 7 de 7
- 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.
article 3 Citação(ões) na Scopus Influence of a hypercholesterolemic diet on the collagen composition of the bladder wall extracellular matrix in rats(2012) NUNES, R. L. V.; BRUSCHINI, H.; UTSUNOMIA, K.; SILVEIRA, M. A.; TEODORO, W. R.; LEITE, K. R. M.; SROUGI, M.Purpose: To investigate the effects of hypercholesterolemic diet on the collagen composition of urinary bladder wall. Materials and methods: Forty-five female 4-week-old Wistar rats were divided into three groups: 1) control group fed a normal diet (ND); 2) model of bladder outlet obstruction (BOO) group fed a ND; and 3) group fed a HCD (1.25% cholesterol). Total serum cholesterol, LDL cholesterol and body weight were assessed at baseline. Four weeks later, group 2 underwent a surgical procedure resulting in a partial BOO, while groups 1 and 3 underwent a sham similar surgical procedure. Six weeks later, all animals had their bladders removed; serum cholesterol and LDL cholesterol levels and body weights were measured. Morphological and morphometric analysis was performed by Picrosirius staining and collagen types I and III were identified by immunofluorescence. Statistical analysis was completed and significance was considered when p<0.05. Results: Rats fed an HCD exhibited a significant increase in LDL cholesterol levels (p<0.001) and body weight (p=0.017), when compared to the groups fed a ND during the ten-week study period. Moreover, the HCD induced morphological alterations of the bladder wall collagen, regarding thin collagen fibers and the amounts of type III collagen when compared to the control group (p=0.002 and p=0.016, respectively), resembling the process promoted in the BOO model. Conclusions: A hyper-cholesterolemic diet in Wistar rats promoted morphological changes of the bladder types of collagen, as well as increases in body weight and LDL cholesterol.article 39 Citação(ões) na Scopus Experimental diabetes modulates collagen remodelling of joints in rats(2012) ATAYDE, Sandra A.; YOSHINARI, Natalino H.; NASCIMENTO, Dafne P.; CATANOZI, Sergio; ANDRADE, Priscila C.; VELOSA, Ana Paula P.; PARRA, Edwin R.; PASSARELLI, Marisa; NAKANDAKARE, Edna R.; CAPELOZZI, Vera L.; TEODORO, Walcy R.The aim of this study was to evaluate extracellular matrix components in articular cartilage, ligaments and synovia in an experimental model of diabetes. Young Wistar rats were divided into a streptozotocin-induced (STZ; 35 mg/kg) diabetic group (DG; n=15) and a control group (CG; n=15). Weight, blood glucose and plasma anti-carboxymethyllysine were measured 70 days after STZ infusions. Knee joints, patellar ligaments, and lateral and medial collateral ligaments were isolated and stained with hematoxylineosin and Picrosirius. The total collagen content was determined by morphometry. Immunofluorescence was employed to evaluate types I, III, and V collagen in ligaments and synovial tissues and types II and XI collagen in cartilage. Results: Higher blood glucose levels and plasma anti-carboxymethyllysine were observed in DG rats when compared to those in CG rats. The final weight was significantly lower in the DG rats than in the CG rats. Histomorphometric evaluation depicted a small quantity of collagen fibers in ligaments and articular cartilage in DG rats, as well as increased collagen in synovial tissue. There was a decrease in cartilage proteoglycans in DG rats when compared with CG rats. Immunofluorescence staining revealed an increase of collagen III and V in ligaments, collagen XI in cartilage, and collagen I in synovial tissue of DG rats compared with CG rats. Conclusion: The ligaments, cartilage and synovia are highly affected following STZ-induced diabetes in rats, due the remodeling of collagen types in these tissues. This process may promote the degradation of the extracellular matrix, thus compromising joint function. Our data may help to better understand the pathogenesis of joint involvement related to diabetes.- 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.
- Photobiomodulation therapy increases collagen II after tendon experimental injury(2021) AKAMATSU, Flayia Emi; TEODORO, Walcy Rosolia; ITEZEROTE, Ana Maria; SILVEIRA, Lizandre Keren Ramos da; SALEH, Samir; MARTINEZ, Carlos Augusto Real; RIBEIRO, Marcelo Lima; PEREIRA, Jose Aires; HOJAIJ, Flavio; ANDRADE, Mauro; JACOMO, Alfredo LuizA tendon is a mechanosensitive tissue that transmits muscle-derived forces to bones. Photobiomodulation (PBM), also known as low-level laser therapy (LLLT), has been used in therapeutic approaches in tendon lesions, but uncertainties regarding its mechanisms of action have prevented its widespread use. We investigated the response of PBM therapy in experimental lesions of the Achilles tendon in rats. Thirty adult male Wistar rats weighing 250 to 300 g were surgically submitted to bilateral partial transverse section of the Achilles tendon. The right tendon was treated with PBM, whereas the left tendon served as a control. On the third postoperative day, the rats were divided into three experimental groups consisting of ten rats each, which were treated with PBM (Konf, Aculas HB 750), 780 nm and 80 mW for 20 seconds, three times/week for 7, 14 and 28 days. The rats were sacrificed at the end of the therapeutic time period. The Sca-1 was examined by immunohistochemistry and histomorphometry, and COLA1, COLA2 and COLA3 gene expression was examined by qRT-PCR. COLA2 gene expression was higher in PBM treated tendons than in the control group. The histomorphometric analysis coincided with increased number of mesenchymal cells, characterized by Sca-1 expression in the lesion region (p<0.001). PBM effectively interferes in tendon tissue repair after injury by stimulating mesenchymal cell proliferation and the synthesis of collagen type II, which is suggested to provide structural support to the interstitial tissues during the healing process of the Achilles tendon. Further studies are needed to confirm the role of PBM in tendon healing.
article 2 Citação(ões) na Scopus Radiofrequency preserves histoarchitecture and enhances collagen synthesis in experimental tendon injury(2016) AKAMATSU, Flavia Emi; SALEH, Samir Omar; HOJAIJ, Flavio; AUGUSTO, Carlos; MARTINEZ, Real; ANDRADE, Mauro; TEODORO, Walcy Rosolia; JACOMO, Alfredo LuizWe investigated the action of radiofrequency (RF) on the healing process after inducing experimental lesions of the Achilles tendon in rats. Wistar rats were surgically subjected to bilateral partial transverse sectioning of the Achilles tendon. The right tendon was treated with radiofrequency (RFT), whereas the left tendon served as a control (CT). On the third postoperative day, the rats were divided into three experimental groups consisting of ten rats each, which were treated with monopolar radiofrequency (Tonederm (TM)) until they were sacrificed on the 7th, 14th or 28th days. The histological specimens were studied for inflammatory cell content, collagen types I and III, immunostaining and morphometry. Total collagen were biochemically analyzed and to evalute fibroblast and myofibroblast proliferation by vimentin and a-actin smooth muscle immunohistochemistry methods. Statistical analysis was performed using the Student's t-test, the sign test and the Kruskal-Wallis test to compare tendons treated with radiofrequency with the non-treated tendons (alpha=5%; alpha=10%). Larger amounts of collagen I with hydroxyproline content and myofibroblast cells were clearly evident within 7 days (p<0.05). No difference was observed in the inflammatory cell content between the groups. We found better collagen arrangement with RF administration across the entire time studied. Radiofrequency administration preserves histoarchitecture and enhances collagen synthesis during the initial phases of cicatrization, suggesting that the treatment can provide improved stiffness during the most vulnerable phases of tendon healing. Clinical studies may include RF among the therapeutic tools in tendinous lesion management.- Adipose-derived stem cells and adipose-derived stem cell-conditioned medium modulate in situ imbalance between collagen I-and collagen V-mediated IL-17 immune response recovering bleomycin pulmonary fibrosis(2020) FELIX, Renato Goncalves; BOVOLATO, Ana Livia Carvalho; COTRIM, Ondina Silvia; LEAO, Patricia dos Santos; BATAH, Sabrina Setembre; GOLIM, Marjorie de Assis; VELOSA, Ana Paula; TEODORO, Walcy; MARTINS, Vanessa; CRUZ, Fernanda Ferreira; DEFFUNE, Elenice; FABRO, Alexandre Todorovic; CAPELOZZI, Vera LuizaThe immunogenic collagen V (Col V) and the proinflammatory cytokine interleukin (IL)-17 have been implicated in the pathogenesis of multiple autoimmune diseases. Col V is also up-regulated during adipogencsis and can stimulate adipocyte differentiation in vitro. Conditioned medium (CM) generated from adipose-derived mesenchymal stem cells (MSCs) reduces bleomycin (BLM)-induced lung injury in rats, suggesting a crucial role in situ of immunomodulatory factors secreted by MSCs in these beneficial effects. In the present work, we investigated this hypothesis, analyzing levels of plasma inflammatory mediators and inflammatory and fibrotic mediators in the lung tissue of BLM-injured rats after treatment with MSCs and CM. Pulmonary fibrosis was intratracheally induced by BLM. After 10 days, BLM animals were further randomized into subgroups receiving saline, MSCs, or CM intravenously. On days 14 and 21, the animals were euthanized, and the lungs were examined through protein expression of nitric oxide synthase (NOS), IL-17, transforming growth factor-beta (TGF-beta), vascular endothelial growth factor, endothelin-1, and the immunogenic Col V through histological quantitative evaluation and plasma levels of fibrinogen, Von Willebrand factor, and platelet-derived growth factor (PDGF). Rats that had been injected with MSCs and CM showed a significant increase in weight and significant improvements at 14 and 21 days after intravenous injection at both time points of analysis of plasma fibrinogen, PDGF, and Von Willebrand factor and NOS-2 expression, supporting an early anti-inflammatory action, thus reducing TGF-beta and collagen I fibers. In contrast, intravenous injection of CM was able to significantly increase the deposition of Col V fibers and IL-17 on both day 14 and day 21 as compared with the amount observed in rats from the BLM group and MSC groups. In conclusion, this study reinforces previous observations on the therapeutic properties of MSCs and CM and is the first report to demonstrate the association of its actions with immunomodulatory biomarkers on lung tissue. We concluded that adipose-derived stem cells and adipose-derived stem cells-CM modulate an in situ imbalance between collagen I- and Col V-mediated IL-17 immune response, emerging as a promising therapeutic option for recovering from BLM pulmonary fibrosis.