Mesenchymal stromal (stem) cell therapy modulates miR-193b5p expression to attenuate sepsis-induced acute lung injury

dc.creatorSantos, Claudia C. dos
dc.creatorAmatullah, Hajera
dc.creatorVaswani, Chirag M.
dc.creatorMaron-Gutierrez, Tatiana
dc.creatorKIm, Michael
dc.creatorMei, Shirley H. J.
dc.creatorSzaszi, Katalin
dc.creatorMonteiro, Ana Paula T.
dc.creatorVarkouhi, Amir K
dc.creatorHerreroz, Raquel
dc.creatorLorente, Jose Angel
dc.creatorTsoporis, James N.
dc.creatorGupta, Sahil
dc.creatorEktesabi, Amin
dc.creatorKavantzas, Nikolaos
dc.creatorSalpeas, Vasileios
dc.creatorMarshall, John C.
dc.creatorRocco, Patricia R.M.
dc.creatorMarsden, Philip A.
dc.creatorWeiss, Daniel J.
dc.creatorStewart, Ducan J.
dc.creatorHu, Pingzhao
dc.creatorLiles, W. Conrad
dc.date2022-06-01T20:36:27Z
dc.date2022-06-01T20:36:27Z
dc.date2022
dc.date.accessioned2023-09-26T21:10:54Z
dc.date.available2023-09-26T21:10:54Z
dc.identifierSANTOS, 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.
dc.identifier0903-1936
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/53045
dc.identifier10.1183/13993003.04216-2020
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8870439
dc.descriptionAlthough 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherERS Publications
dc.rightsopen access
dc.subjectTerapia
dc.subjectCélulas mesenquimais estromais
dc.subjectModula expressão de miR-193b-5p
dc.subjectAtenuar a lesão pulmonar aguda
dc.subjectInduzida por sepse
dc.subjectMesenchymal stromal (stem)
dc.subjectCell therapy
dc.subjectModulates miR-193b- 5p expression
dc.subjectAttenuate
dc.subjectAcute lung injury
dc.subjectSepsis-induced
dc.titleMesenchymal stromal (stem) cell therapy modulates miR-193b5p expression to attenuate sepsis-induced acute lung injury
dc.typeArticle


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