Bone marrow mononuclear cells attenuate fibrosis development after severe acute kidney injury
Autor(a) principal: | |
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Data de Publicação: | 2010 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | https://dx.doi.org/10.1038/labinvest.2010.45 https://repositorio.unifesp.br/handle/11600/32485 |
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. |
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Bone marrow mononuclear cells attenuate fibrosis development after severe acute kidney injuryMesenchymal stem cellAcute kidney injuryIschemia-reperfusion injuryFibrosisInflammationBone marrowOne 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.Univ São Paulo, Inst Biomed Sci 4, Dept Immunol, Lab Transplantat Immunobiol, BR-05508900 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Div Nephrol, Expt & Clin Immunol Lab, São Paulo, BrazilUniv São Paulo, Dept Pathol, BR-05508900 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Div Nephrol, Expt & Clin Immunol Lab, São Paulo, BrazilWeb of ScienceFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)INCT Complex FluidsDECIT/Ministério da SaúdeFAPESP: 06/00620-5FAPESP: 04/08226-9FAPESP: 07/07139-3CNPq: 04113826-5Nature Publishing GroupUniversidade de São Paulo (USP)Universidade Federal de São Paulo (UNIFESP)Semedo, Patricia [UNIFESP]Donizetti-Oliveira, Cassiano [UNIFESP]Burgos-Silva, Marina [UNIFESP]Cenedeze, Marco Antonio [UNIFESP]Malheiros, Denise Maria Avancini CostaPacheco-Silva, Alvaro [UNIFESP]Camara, Niels Olsen Saraiva [UNIFESP]2016-01-24T13:59:36Z2016-01-24T13:59:36Z2010-05-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion685-695https://dx.doi.org/10.1038/labinvest.2010.45Laboratory Investigation. New York: Nature Publishing Group, v. 90, n. 5, p. 685-695, 2010.10.1038/labinvest.2010.450023-6837https://repositorio.unifesp.br/handle/11600/32485WOS:000277170000004engLaboratory Investigationinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2022-07-20T19:20:52Zoai:repositorio.unifesp.br/:11600/32485Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652022-07-20T19:20:52Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.none.fl_str_mv |
Bone marrow mononuclear cells attenuate fibrosis development after severe acute kidney injury |
title |
Bone marrow mononuclear cells attenuate fibrosis development after severe acute kidney injury |
spellingShingle |
Bone marrow mononuclear cells attenuate fibrosis development after severe acute kidney injury Semedo, Patricia [UNIFESP] Mesenchymal stem cell Acute kidney injury Ischemia-reperfusion injury Fibrosis Inflammation Bone marrow |
title_short |
Bone marrow mononuclear cells attenuate fibrosis development after severe acute kidney injury |
title_full |
Bone marrow mononuclear cells attenuate fibrosis development after severe acute kidney injury |
title_fullStr |
Bone marrow mononuclear cells attenuate fibrosis development after severe acute kidney injury |
title_full_unstemmed |
Bone marrow mononuclear cells attenuate fibrosis development after severe acute kidney injury |
title_sort |
Bone marrow mononuclear cells attenuate fibrosis development after severe acute kidney injury |
author |
Semedo, Patricia [UNIFESP] |
author_facet |
Semedo, Patricia [UNIFESP] Donizetti-Oliveira, Cassiano [UNIFESP] Burgos-Silva, Marina [UNIFESP] Cenedeze, Marco Antonio [UNIFESP] Malheiros, Denise Maria Avancini Costa Pacheco-Silva, Alvaro [UNIFESP] Camara, Niels Olsen Saraiva [UNIFESP] |
author_role |
author |
author2 |
Donizetti-Oliveira, Cassiano [UNIFESP] Burgos-Silva, Marina [UNIFESP] Cenedeze, Marco Antonio [UNIFESP] Malheiros, Denise Maria Avancini Costa Pacheco-Silva, Alvaro [UNIFESP] Camara, Niels Olsen Saraiva [UNIFESP] |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade de São Paulo (USP) Universidade Federal de São Paulo (UNIFESP) |
dc.contributor.author.fl_str_mv |
Semedo, Patricia [UNIFESP] Donizetti-Oliveira, Cassiano [UNIFESP] Burgos-Silva, Marina [UNIFESP] Cenedeze, Marco Antonio [UNIFESP] Malheiros, Denise Maria Avancini Costa Pacheco-Silva, Alvaro [UNIFESP] Camara, Niels Olsen Saraiva [UNIFESP] |
dc.subject.por.fl_str_mv |
Mesenchymal stem cell Acute kidney injury Ischemia-reperfusion injury Fibrosis Inflammation Bone marrow |
topic |
Mesenchymal stem cell Acute kidney injury Ischemia-reperfusion injury Fibrosis Inflammation Bone marrow |
description |
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. |
publishDate |
2010 |
dc.date.none.fl_str_mv |
2010-05-01 2016-01-24T13:59:36Z 2016-01-24T13:59:36Z |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://dx.doi.org/10.1038/labinvest.2010.45 Laboratory Investigation. New York: Nature Publishing Group, v. 90, n. 5, p. 685-695, 2010. 10.1038/labinvest.2010.45 0023-6837 https://repositorio.unifesp.br/handle/11600/32485 WOS:000277170000004 |
url |
https://dx.doi.org/10.1038/labinvest.2010.45 https://repositorio.unifesp.br/handle/11600/32485 |
identifier_str_mv |
Laboratory Investigation. New York: Nature Publishing Group, v. 90, n. 5, p. 685-695, 2010. 10.1038/labinvest.2010.45 0023-6837 WOS:000277170000004 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Laboratory Investigation |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
685-695 |
dc.publisher.none.fl_str_mv |
Nature Publishing Group |
publisher.none.fl_str_mv |
Nature Publishing Group |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
biblioteca.csp@unifesp.br |
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1814268406500687872 |