EDWIN ROGER PARRA CUENTAS
Projetos de Pesquisa
Unidades Organizacionais
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
- Usual interstitial pneumonia and smoking-related interstitial fibrosis display epithelial to mesenchymal transition in fibroblastic foci(2014) FABRO, Alexandre Todorovic; MINATEL, Igor Otavio; RANGEL, Maristela Peres; HALBWEDL, Iris; PARRA, Edwin Roger; CAPELOZZI, Vera Luiza; POPPER, HelmutBackground: Fibroblastic foci (FF) are a major histological feature of usual interstitial pneumonia (UIP) in idiopathic pulmonary fibrosis (IPF) and collagen vascular diseases (non-IPF). In addition, FF are occasionally associated with smoking-related interstitial fibrosis (SRIF). Recent studies have suggested a role for epithelial to mesenchymal transition (EMT) in pulmonary fibrogenesis. Methods: Here, we investigated whether EMT was present in patients with IPF (n = 19), non-IPF (n = 17), and SRIF (n = 16) using morphometric immunohistochemistry, electron microscopy, and confocal microscopy. All patients had received lung biopsies or lobectomies for lung cancer. Results: IPF and non-IPF patients displayed restrictive lung function patterns, whereas those with SRIF presented mixed patterns. Cells within FF presented high number of alpha-smooth muscle actin (alpha SMA)-staining cells; however, the foci of IPF patients showed comparatively lower number. Moreover, colocalization of thyroid transcription factor-1 (TTF1) and alpha SMA within FF showed low number of staining cells for IPF and SRIF in comparison to non-IPF (p < 0.01). Nevertheless, all groups displayed colocalization of high rate of TTF1(+)-cells and low rate of alpha SMA(+)-cells within hyperplastic epithelioid cells in FF. Also, we observed areas with low proportion of TTF1(+) cells and alpha SMA(+) cells, which were present in SRIF and non-IPF more often than IPF (p < 0.001). Electron microscopy revealed small breaks in the alveolar basal lamina, which allowed epithelioid cells to directly contact the collagenous matrix and fibroblasts. Three-dimensional reconstruction revealed intense alpha SMA staining within some epithelioid cells, suggesting that they had gained a mesenchymal phenotype. Conclusions: These findings constitute the first report of EMT in SRIF and suggest that EMT occurs more prominently in SRIF and non-IPF than IPF.
conferenceObject Epithelial mesenchymal transition in fibroblastic foci of different fibrosing lung diseases: Repair or remodeling?(2013) FABRO, Alexandre Todorovic; HALBWEDL, Iris; PARRAS, Edwin Roger; CAPELOZZI, Vera Luiza; POPPER, HelmutconferenceObject Collagen V Maintains Experimental Pulmonary Fibrosis In Il17-dependent And -Independent Pathways(2013) FABRO, A. T.; SILVA, P. Q.; ZOCOLARO, W. S.; ALMEIDA, M. S.; MINATEL, I. O.; PRANDO, E. C.; RAINHO, C. A.; VELOSA, A. P.; TEODORO, W. R.; PARRA-CUENTAS, E. R.; POPPER, H. H.; CAPELOZZI, V. L.conferenceObject Late Stage of Experimental Pulmonary Fibrosis is Modulated by Collagen V(2012) FABRO, A. T.; MINATEL, I. O.; TEODORO, W. R.; CUENTAS, E. R. Parra; RAINHO, C. A.; CAPELOZZI, V. L.; POPPER, H.Background: The late phase of experimental models of pulmonary fibrosis (PF) tend to recover from fibrotic process, but in different degrees depending on the drug/strain/inflammation. The mechanisms which prolong the process in the late phase in certain strains may participate in the PF. Aim: To determine the immune-fibrotic pattern in pulmonary fibrosis models in the late stage (21 days). Methods: The PF was induced in Bleomycin (BLM-BALB) and Paraquat (PQ-BALB) Balb/c and IL17-RA-Knockout (BLM-IL17KO-C57) and wild C57/B6 (BLM-C57). We used the picrosirius-polarization method and immunofluorescence to morphometrically study peribronchiolar (PB) and peripherical (PP) collagen fibers and collagen III and V, respectively. The results of collagens were confirmed by RT-PCR of cultured pulmonary fibroblasts. Results: The late PQ and BLM-mediated peribronchiolar fibrosis is IL-17 independent, as IL17-RA)/) mice developed similar PB after induction when compared to BLM-BALB, PQ-BALB and BLM-C57. The level of gene expression of collagen I and III did not show differences between the groups of the cultures, validating our results. However, the PP was higher in the C57BL/6, independent of the absence of IL-17RA. The protein expression of Col5 was higher in IL-17RA-KO and lower in BLM-Balb/c. Like-wise, the gene expression of Col5 was higher in IL17RA-KO and lower in BLM-Balb/c. Conclusion: The perpetuation of PF in fibrosis-susceptible mice can be modulated by Col5 in a IL-17ReceptorA-independent manner in the late phase. However, the IL-17 pattern appears to influence the expression of collagen V. This suggests that exposure of the collagen V from the basement membrane is an important component responsible for PF.- The Th17 pathway in the peripheral lung microenvironment interacts with expression of collagen V in the late state of experimental pulmonary fibrosis(2015) FABRO, Alexandre T.; SILVA, Pedro H. R. Q. da; ZOCOLARO, William S.; ALMEIDA, Mozar S. de; RANGEL, Maristela P.; OLIVEIRA, Cristiano C. de; MINATEL, Igor O.; PRANDO, Erika d. C.; RAINHO, Claudia A.; TEODORO, Walcy R.; VELOSA, Ana P. P.; SABER, Alexandre M. A.; PARRA-CUENTAS, Edwin R.; POPPER, Helmut H.; CAPELOZZI, Vera L.Background: Myofibroblasts derived from fibroblasts in the pathogenesis of pulmonary fibrosis causes excessive and disordered deposition of matrix proteins, including collagen V, which can cause a Th17-mediated immune response and lead to apoptosis. However, whether the intrinsic ability of lung FBs to produce the matrix depends on their site-specific variations is not known. Aim: To investigate the link between Th17 and collagen V that maintains pulmonary remodeling in the peripheral lung microenvironment during the late stage of experimental pulmonary fibrosis. Methods: Young male mice including wild Balb/c mice (BALB, n = 10), wild C57 Black/6J mice (C57, n = 10) and IL-17 receptor A knockout mice (KO, n = 8), were sacrificed 21 days after treatment with bleomycin. Picrosirius red staining, immunohistochemistry for IL-17-related markers and ""in situ"" detection of apoptosis, immunofluorescence for collagen types I and V, primary cell cultures from tissue lung explants for RT-PCR and electron microscopy were used. Results: The peripheral deposition of extracellular matrix components by myofibroblasts during the late stage is maintained in C57 mice compared with that in Balb mice and is not changed in the absence of IL-17 receptor A; however, the absence of IL-17 receptor A induces overexpression of type V collagen, amplifies the peripheral expression of IL-17 and IL-17-related cytokines and reduces peripheral lung fibroblast apoptosis. Conclusion: A positive feedback loop between the expression patterns of collagen V and IL-17 may coordinate the maintenance of peripheral collagen I in the absence of IL-17 receptor A in fibrosis-susceptible strains in a site-specific manner.
conferenceObject Late stage of experimental pulmonary fibrosis is modulated by collagen V(2012) FABRO, Alexandre Todorovic; ALMEIDA, Mozar Suzigan de; MINATEL, Igor O.; PRADO, Erika C.; RAINHO, Claudia Aparecida; WALCY, P. R. Teodoro; CUENTAS, Edwin R. Parra; CAPELOZZI, Vera; POPPER, Helmut