| Author | Santos, Claudia C. dos | |
| Author | Amatullah, Hajera | |
| Author | Vaswani, Chirag M. | |
| Author | Maron-Gutierrez, Tatiana | |
| Author | KIm, Michael | |
| Author | Mei, Shirley H. J. | |
| Author | Szaszi, Katalin | |
| Author | Monteiro, Ana Paula T. | |
| Author | Varkouhi, Amir K | |
| Author | Herreroz, Raquel | |
| Author | Lorente, Jose Angel | |
| Author | Tsoporis, James N. | |
| Author | Gupta, Sahil | |
| Author | Ektesabi, Amin | |
| Author | Kavantzas, Nikolaos | |
| Author | Salpeas, Vasileios | |
| Author | Marshall, John C. | |
| Author | Rocco, Patricia R.M. | |
| Author | Marsden, Philip A. | |
| Author | Weiss, Daniel J. | |
| Author | Stewart, Ducan J. | |
| Author | Hu, Pingzhao | |
| Author | Liles, W. Conrad | |
| Access date | 2022-06-01T20:36:27Z | |
| Available date | 2022-06-01T20:36:27Z | |
| Document date | 2022 | |
| Citation | SANTOS, Claudia C. dos et al. Mesenchymal stromal (stem) cell therapy modulates miR-193b- 5p expression to attenuate sepsis-induced acute lung injury. European Respiratory Journal, v. 59, 2004216, p. 1 - 15, 2022. | pt_BR |
| ISSN | 0903-1936 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/53045 | |
| Language | eng | pt_BR |
| Publisher | ERS Publications | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Terapia | pt_BR |
| Subject in Portuguese | Células mesenquimais estromais | pt_BR |
| Subject in Portuguese | Modula expressão de miR-193b-5p | pt_BR |
| Subject in Portuguese | Atenuar a lesão pulmonar aguda | pt_BR |
| Subject in Portuguese | Induzida por sepse | pt_BR |
| Title | Mesenchymal stromal (stem) cell therapy modulates miR-193b5p expression to attenuate sepsis-induced acute lung injury | pt_BR |
| Type | Article | |
| DOI | 10.1183/13993003.04216-2020 | |
| Abstract | Although mesenchymal stromal (stem) cell (MSC) administration attenuates sepsis-induced lung injury in
pre-clinical models, the mechanism(s) of action and host immune system contributions to its therapeutic
effects remain elusive. We show that treatment with MSCs decreased expression of host-derived
microRNA (miR)-193b-5p and increased expression of its target gene, the tight junctional protein occludin
(Ocln), in lungs from septic mice. Mutating the Ocln 3′ untranslated region miR-193b-5p binding
sequence impaired binding to Ocln mRNA. Inhibition of miR-193b-5p in human primary pulmonary
microvascular endothelial cells prevents tumour necrosis factor (TNF)-induced decrease in Ocln gene and
protein expression and loss of barrier function. MSC-conditioned media mitigated TNF-induced miR-
193b-5p upregulation and Ocln downregulation in vitro. When administered in vivo, MSC-conditioned
media recapitulated the effects of MSC administration on pulmonary miR-193b-5p and Ocln expression.
MiR-193b-deficient mice were resistant to pulmonary inflammation and injury induced by
lipopolysaccharide (LPS) instillation. Silencing of Ocln in miR-193b-deficient mice partially recovered the
susceptibility to LPS-induced lung injury. In vivo inhibition of miR-193b-5p protected mice from
endotoxin-induced lung injury. Finally, the clinical significance of these results was supported by the
finding of increased miR-193b-5p expression levels in lung autopsy samples from acute respiratory distress
syndrome patients who died with diffuse alveolar damage. | pt_BR |
| Affilliation | The Keenan Research Centre for Biomedical Science of St Michael’s Hospital. Toronto, ON, Canada / Dept of Physiology, Temerty Faculty of Medicine, University of Toronto. Toronto, ON, Canada / Institute of Medical Sciences and Interdepartmental Division of Critical Care, Temerty Faculty of Medicine, University of Toronto.Toronto, ON, Canada. | pt_BR |
| Affilliation | The Keenan Research Centre for Biomedical Science of St Michael’s Hospital. Toronto, ON, Canada. | pt_BR |
| Affilliation | The Keenan Research Centre for Biomedical Science of St Michael’s Hospital. Toronto, ON, Canada / Dept of Physiology, Temerty Faculty of Medicine, University of Toronto. Toronto, ON, Canada. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | The Keenan Research Centre for Biomedical Science of St Michael’s Hospital. Toronto, ON, Canada. | pt_BR |
| Affilliation | Regenerative Medicine Program, Ottawa Hospital Research Institute. Ottawa, ON, Canada. | pt_BR |
| Affilliation | The Keenan Research Centre for Biomedical Science of St Michael’s Hospital. Toronto, ON, Canada / Dept of Surgery. University of Toronto, Toronto, ON, Canada. | pt_BR |
| Affilliation | The Keenan Research Centre for Biomedical Science of St Michael’s Hospital. Toronto, ON, Canada. | pt_BR |
| Affilliation | The Keenan Research Centre for Biomedical Science of St Michael’s Hospital. Toronto, ON, Canada. | pt_BR |
| Affilliation | University Hospital of Getafe, Critical Care Dept. Madrid, Spain. | pt_BR |
| Affilliation | University Hospital of Getafe, Critical Care Dept. Madrid, Spain / Centros de Investigación Biomédica en Red (CIBER) de Enfermedades Respiratorias. Madrid, Spain / Universidad Europea de Madrid. Madrid, Spain.. | pt_BR |
| Affilliation | The Keenan Research Centre for Biomedical Science of St Michael’s Hospital. Toronto, ON, Canada. | pt_BR |
| Affilliation | The Keenan Research Centre for Biomedical Science of St Michael’s Hospital. Toronto, ON, Canada / Institute of Medical Sciences and Interdepartmental Division of Critical Care, Temerty Faculty of Medicine, University of Toronto. Toronto, ON, Canada. | pt_BR |
| Affilliation | The Keenan Research Centre for Biomedical Science of St Michael’s Hospital. Toronto, ON, Canada / Institute of Medical Sciences and Interdepartmental Division of Critical Care, Temerty Faculty of Medicine, University of Toronto. Toronto, ON, Canada. | pt_BR |
| Affilliation | 1st Dept of Pathology, School of Medicine, National and Kapodistrian, University of Athens. Athens, Greece. | pt_BR |
| Affilliation | 1st Dept of Pathology, School of Medicine, National and Kapodistrian, University of Athens. Athens, Greece. | pt_BR |
| Affilliation | The Keenan Research Centre for Biomedical Science of St Michael’s Hospital. Toronto, ON, Canada / Institute of Medical Sciences and Interdepartmental Division of Critical Care, Temerty Faculty of Medicine, University of Toronto. Toronto, ON, Canada / Dept of Surgery, University of Toronto. Toronto, ON, Canada. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofisica Carlos Chagas Filho. Laboratório de Investigação Pulmonar. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | The Keenan Research Centre for Biomedical Science of St Michael’s Hospital. Toronto, ON, Canada. | pt_BR |
| Affilliation | Dept of Medicine, University of Vermont, Burlington, VT, USA. | pt_BR |
| Affilliation | Regenerative Medicine Program, Ottawa Hospital Research Institute. Ottawa, ON, Canada. | pt_BR |
| Affilliation | Dept of Biochemistry and Medical Genetics, University of Manitoba. Winnipeg, MB, Canada. | pt_BR |
| Affilliation | Dept of Medicine, University of Washington, Seattle, WA, USA. | pt_BR |
| Subject | Mesenchymal stromal (stem) | pt_BR |
| Subject | Cell therapy | pt_BR |
| Subject | Modulates miR-193b- 5p expression | pt_BR |
| Subject | Attenuate | pt_BR |
| Subject | Acute lung injury | pt_BR |
| Subject | Sepsis-induced | pt_BR |
