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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Bone marrow mononuclear cells attenuate fibrosis development after severe acute kidney injury

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Autor(es):
Semedo, Patricia [1] ; Donizetti-Oliveira, Cassiano [1] ; Burgos-Silva, Marina [1] ; Cenedeze, Marco Antonio [1] ; Avancini Costa Malheiros, Denise Maria [2] ; Pacheco-Silva, Alvaro [1] ; Saraiva Camara, Niels Olsen [3, 1]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Univ Fed Sao Paulo, Escola Paulista Med, Div Nephrol, Expt & Clin Immunol Lab, Sao Paulo - Brazil
[2] Univ Sao Paulo, Dept Pathol, BR-05508900 Sao Paulo - Brazil
[3] Univ Sao Paulo, Inst Biomed Sci 4, Dept Immunol, Lab Transplantat Immunobiol, BR-05508900 Sao Paulo - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: LABORATORY INVESTIGATION; v. 90, n. 5, p. 685-695, MAY 2010.
Citações Web of Science: 25
Resumo

One of the early phases that lead to fibrosis progression is inflammation. Once this stage is resolved, fibrosis might be prevented. Bone marrow mononuclear cells (BMMCs) are emerging as a new therapy for several pathologies, including autoimmune diseases, because they enact immunosuppression. In this study we aimed to evaluate the role of BMMC administration in a model of kidney fibrosis induced by an acute injury. C57Bl6 mice were subjected to unilateral severe ischemia by clamping the left renal pedicle for 1 h. BMMCs were isolated from femurs and tibia, and after 6 h of reperfusion, 1 x 10(6) cells were administrated intraperitoneally. At 24 h after surgery, treated animals showed a significant decrease in creatinine and urea levels when compared with untreated animals. Different administration routes were tested. Moreover, interferon (IFN) receptor knockout BMMCs were used, as this receptor is necessary for BMMC activation. Labeled BMMCs were found in ischemic kidney on FACS analysis. This improved outcome was associated with modulation of inflammation in the kidney and systemic modulation, as determined by cytokine expression profiling. Despite non-amelioration of functional parameters, kidney mRNA expression of interleukin (IL)-6 at 6 weeks was lower in BMMC-treated animals, as were levels of collagen 1, connective tissue growth factor (CTGF), transforming growth factor-beta (TGF-beta) and vimentin. Protective molecules, such as IL-10, heme oxygenase 1 (HO-1) and bone morphogenetic 7 (BMP-7), were increased in treated animals after 6 weeks. Moreover, Masson and Picrosirius red staining analyses showed less fibrotic areas in the kidneys of treated animals. Thus, early modulation of inflammation by BMMCs after an ischemic injury leads to reduced fibrosis through modulation of early inflammation. (AU)

Processo FAPESP: 07/07139-3 - Investigando o papel da heme-oxigenase 1 em diferentes processos inflamatórios renais em modelos animais
Beneficiário:Niels Olsen Saraiva Câmara
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 04/08226-9 - Tolerância imunológica em transplante renal: papel das células reguladoras
Beneficiário:Niels Olsen Saraiva Câmara
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 06/00620-5 - Análise dos células tronco mesenquimais em modelos de isquemia renal aguda e crônica
Beneficiário:Patricia Semedo Kuriki
Linha de fomento: Bolsas no Brasil - Doutorado