HUMBERTO DELLE
Projetos de Pesquisa
Unidades Organizacionais
LIM/29 - Laboratório de Nefrologia Celular, Genética e Molecular, Hospital das Clínicas, Faculdade de Medicina
5 resultados
Resultados de Busca
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conferenceObject Effects of Human Amniotic Fluid Stem Cells in a Model of Aorta Allograft Vasculopathy(2012) SANTANA, A. C.; DELLE, H.; CAVAGLIERI, R. C.; LOPES, M. A. B.; FRANCISCO, R. P. V.; ZUGAIB, M.; BYDLOWSKI, S. P.; NORONHA, I. L.Chronic allograft vasculopathy (CAV) is an important cause of graft loss. Considering the immune-in flammatory events involved in the development of CAV, therapeutic approaches to target this process are of relevance. Human amniotic fluid derived stem cells (hAFSC), a class of fetal, pluripotent stem cells with intermediate characteristics between embryonic and adult stem cells display immunomodulatory properties. hAFSC express mesenchymal and embryonic markers, show high proliferation rates, but do not induce tumor formation and their use does not raise ethical issues. Thus, we sought to investigate the effect of hAFSC on CAV in a model of aorta transplantation. Orthotopic aorta transplantation was performed using Fisher (F344) rats as donors and Lewis rats as recipients. Rats were divided into 3 groups: syngeneic (SYNG), untreated F344 receiving aorta from F344 (n=8); allogeneic (ALLO), Lewis rats receiving allogeneic aorta from F344 (n=8); and ALLO+hAFSC, ALLO rats treated with hAFSC (106 cells) (n=8). Histological analysis and immunohistochemistry were performed 30 days post transplantation. ALLO developed a robust aortic neointimal formation, accompanied by a high number of ED1+ and CD43+ cells, and enhanced expression of α-SMA in theneointima. Treatment with hAFSC diminished neointimal thickness and induced a significant decrease of ED1+, CD43+ cells and α-SMA expression in the neointima. Comparative analyses in the differents groups PARAMETERS SYNG ALLO ALLO+hAFSC Neointima thickness (μm) 0±0 208.7±25.4* 180.7±23.7* ED-1+ (cells/mm2) 0±0 4.845±841* 1.100±276*, #CD43+ (cells/mm2) 0±0 4.064±563* 1.080±309*,#α-SMA (%) 0±0 25±6* 8±3*, #*p<0.05 vs. SYNG; #P<0.05 vs. ALLO These preliminary results showed that hAFSC suppressed inflammation and myofibroblast migration to the intima, which may contribute to ameliorate vascular changes in CAV.- Antifibrotic Effect of Tamoxifen in a Model of Progressive Renal Disease(2012) DELLE, Humberto; ROCHA, Jose Roberto C.; CAVAGLIERI, Rita C.; VIEIRA JR., Jose Mauro; MALHEIROS, Denise M. A. C.; NORONHA, Irene L.Tamoxifen, a selective estrogen receptor modulator, has antifibrotic properties; however, whether it can attenuate renal fibrosis is unknown. In this study, we tested the effects of tamoxifen in a model of hypertensive nephrosclerosis (chronic inhibition of nitric oxide synthesis with L-NAME). After 30 days, treated rats had significantly lower levels of albuminuria as well as lower histologic scores for glomerulosclerosis and interstitial fibrosis than untreated controls. Tamoxifen was renoprotective despite having no effect on the sustained, severe hypertension induced by L-NAME. Tamoxifen prevented the accumulation of extracellular matrix by decreasing the expression of collagen I, collagen III, and fibronectin mRNA and protein. These renoprotective effects associated with inhibition of TGF-beta 1 and plasminogen activator inhibitor-1, and with a significant reduction in a-smooth muscle actin-positive cells in the renal interstitium. Furthermore, tamoxifen abrogated IL-1 beta- and angiotensin-II-induced proliferation of fibroblasts from both kidney explants and from the NRK-49F cell line. Tamoxifen also inhibited the expression of extracellular matrix components and the production and release of TGF-beta 1 into the supernatant of these cells. In summary, tamoxifen exhibits antifibrotic effects in the L-NAME model of hypertensive nephrosclerosis, likely through the inhibition of TGF-beta 1, suggesting that it may have therapeutic use in CKD treatment.
conferenceObject Human Amniotic Fluid Stem Cells Reduce Neointimal Formation and Inflammation in a Model of Aortic Allograft Vasculopathy(2012) SANTANA, A. C.; CAVAGLIERI, R. C.; DELLE, H.; LOPES, M. A. B.; V, R. P. Francisco; ZUGAIB, M.; BYDLOWSKI, S. P.; NORONHA, I. L.- Protective Effects of Human Amniotic Fluid Stem Cells in a Model of Aorta Allograft Vasculopathy in Rats(2012) SANTANA, A. C.; DELLE, H.; CAVAGLIERI, R. C.; LOPES, M. A. B.; FRANCISCO, R. P. V.; ZUGAIB, M.; BYDLOWSKI, S. P.; NORONHA, I. L.Background. Chronic allograft vasculopathy (CAV) is an important cause of graft loss. Considering the immune inflammatory events involved in the development of CAV, therapeutic approaches to target this process are of relevance. Human amniotic fluid derived stem cells (hAFSCs), a class of fetal, pluripotent stem cells with intermediate characteristics between embryonic and adult stem cells, display immunomodulatory properties. hAFSCs express mesenchymal and embryonic markers, show high proliferation rates; however, they do not induce tumor formation, and their use does not raise ethical issues. Thus, we sought to investigate the effect of hAFSC on CAV in a model of aorta transplantation. Methods. Orthotopic aorta transplantation was performed using Fisher (F344) rats as donors and Lewis rats as recipients. Rats were divided into three groups: syngeneic (SYNG), untreated F344 receiving aorta from F344 (n = 8); allogeneic (ALLO), Lewis rats receiving allogeneic aorta from F344 (n = 8); and ALLO + hAFSC, ALLO rats treated with hAFSC (10(6) cells; n = 8). Histological analysis and immunohistochemistry were performed 30 days posttransplantation. Results. The ALLO group developed a robust aortic neointimal formation (208.7 +/- 25.4 gm) accompanied by a significant high number of ED1(+) (4845 +/- 841 cells/mm(2)) and CD43(+) cells (4064 +/- 563 cells/mm(2)), and enhanced expression of a-smooth muscle actin in the neointima (25 +/- 6%). Treatment with hAFSC diminished neointimal thickness (180.7 +/- 23.7 mu m) and induced a significant decrease of ED1(+) (1100 +/- 276 cells/mm(2)), CD43(+) cells (1080 +/- 309 cells/mu m(2)), and alpha-smooth muscle actin expression 8 +/- 3% in the neointima. Conclusions. These preliminary results showed that hAFSC suppressed inflammation and myofibroblast migration to the intima, which may contribute to ameliorate vascular changes in CAV.
- Thalidomide suppresses inflammation in adenine-induced CKD with uraemia in mice(2013) SANTANA, Alexandre C.; DEGASPARI, Sabrina; CATANOZI, Sergio; DELLE, Humberto; LIMA, Larissa De Sa; SILVA, Cleonice; BLANCO, Paula; SOLEZ, Kim; SCAVONE, Cristoforo; NORONHA, Irene L.Persistent systemic inflammation has been widely recognized in patients with chronic kidney disease (CKD), and is associated with increased risk of morbidity and mortality. Intervention therapies aiming for the blockade of inflammatory cytokines are considered attractive approaches for CKD patients with signs of chronic inflammation. In this context, thalidomide, due to its potent anti-inflammatory and immunomodulatory properties, may represent an alternative strategy of treatment. In the present study, we developed an experimental model of CKD with uraemia in mice, induced by a diet rich in adenine, which causes progressive renal dysfunction, resembling the human uraemic features. Inflammatory parameters were analysed in this model of CKD and the potential beneficial effects of thalidomide as an anti-inflammatory drug was also investigated. C57/BL-6 mice were fed with an adenine-containing diet during a period of 6 weeks. Thirty mice were divided into three groups: Control group (animals receiving normal diet), ADE group (mice receiving adenine-containing diet) and ADE TLD group (CKD mice receiving thalidomide, 30 mg/kg/day, by gavage). Besides biochemical and histopathological changes, local and systemic inflammatory parameters were also analysed, including expression of cytokines interleukin (IL)-1, tumour necrosis factor-, IL-6, IL-4 and IL-10 in kidney samples by real-time RTPCR and quantification of serum levels of cytokines. Finally, the electrophoretic mobility shift assay (EMSA) for NF-B was also examined. Adenine-fed mice developed advanced CKD characterized by a marked increase in serum urea, creatinine, phosphorus and intact parathyroid hormone (iPTH) levels. In addition, histological changes of tubulointerstitial injury, characterized by deposition of crystals in the kidney, accompanied by tubular dilatation, degeneration of proximal tubular epithelium with loss of the brush border, inflammatory cellular infiltration, foreign-body granuloma formation and interstitial fibrosis were also evident. By immunohistochemistry, Mac-2- and -SMA-positive cells were identified in the tubulointerstitial compartment. Treatment with thalidomide significantly reduced serum urea, creatinine, phosphorus and iPTH levels and protected against tubulointerstitial injury. Local and systemic inflammation in the mice model of adenine-induced CKD was confirmed by the findings of significantly high expression of cytokine mRNA levels and NF-B activation in the kidney tissue as well as marked increased serum levels of in?ammatory cytokines. Thalidomide treatment significantly reduced gene expression of these cytokines and the activation of the NF-B in the renal tissue and the circulating levels of cytokines. Dietary adenine caused advanced CKD with uraemia in mice providing a useful experimental model to study molecular and morphological changes associated with this disease. The negative impact of inflammation in this CKD model was overcome by the marked anti-inflammatory effects of thalidomide, promoting renal protection.