Cargando…
miRNAs Potentially Involved in Post Lung Transplant-Obliterative Bronchiolitis: The Role of miR-21-5p
Epigenetic changes, including miRNAs deregulation, have been suggested to play a significant role in development of obliterative bronchiolitis (OB) in transplanted lungs. Many studies have tried to identify ideal candidate miRNAs and the downstream pathways implicated in the bronchiolar fibro-oblite...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003603/ https://www.ncbi.nlm.nih.gov/pubmed/33804639 http://dx.doi.org/10.3390/cells10030688 |
_version_ | 1783671728597106688 |
---|---|
author | Bozzini, Sara Pandolfi, Laura Rossi, Elena Inghilleri, Simona Zorzetto, Michele Ferrario, Giuseppina Di Carlo, Stefano Politano, Gianfranco De Silvestri, Annalisa Frangipane, Vanessa Porzio, Michele Kessler, Romain Calabrese, Fiorella Meloni, Federica Morbini, Patrizia |
author_facet | Bozzini, Sara Pandolfi, Laura Rossi, Elena Inghilleri, Simona Zorzetto, Michele Ferrario, Giuseppina Di Carlo, Stefano Politano, Gianfranco De Silvestri, Annalisa Frangipane, Vanessa Porzio, Michele Kessler, Romain Calabrese, Fiorella Meloni, Federica Morbini, Patrizia |
author_sort | Bozzini, Sara |
collection | PubMed |
description | Epigenetic changes, including miRNAs deregulation, have been suggested to play a significant role in development of obliterative bronchiolitis (OB) in transplanted lungs. Many studies have tried to identify ideal candidate miRNAs and the downstream pathways implicated in the bronchiolar fibro-obliterative process. Several candidate miRNAs, previously indicated as possibly being associated with OB, were analyzed by combining the quantitative real time-polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH) of lung tissues of OB affected patients. Disease and OB-lesion-specific expression of miR-21-5p was confirmed and by computational analysis we were able to identify the network of genes most probably associated miR-21-5p in the context of OB fibrogenesis. Among all potentially associated genes, STAT3 had a very high probability score. Immunohistochemistry showed that STAT3/miR-21-5p were co-over expressed in OB lesions, thus, suggesting miR-21-5p could regulate STAT3 expression. However, miR-21-5p inhibition in cultures of bronchiolitis obliterans syndrome (BOS) derived myofibroblasts did not significantly affect STAT3 mRNA and protein expression levels. This study demonstrates the specificity of miR-21-5p over-expression in OB lesions and contributes to existing knowledge on the miR-21-5p downstream pathway. Activation of STAT3 is associated with miR-21-5p upregulation, however, STAT-3 network activation is most likely complex and miR-21-5p is not the sole regulator of STAT3. |
format | Online Article Text |
id | pubmed-8003603 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-80036032021-03-28 miRNAs Potentially Involved in Post Lung Transplant-Obliterative Bronchiolitis: The Role of miR-21-5p Bozzini, Sara Pandolfi, Laura Rossi, Elena Inghilleri, Simona Zorzetto, Michele Ferrario, Giuseppina Di Carlo, Stefano Politano, Gianfranco De Silvestri, Annalisa Frangipane, Vanessa Porzio, Michele Kessler, Romain Calabrese, Fiorella Meloni, Federica Morbini, Patrizia Cells Article Epigenetic changes, including miRNAs deregulation, have been suggested to play a significant role in development of obliterative bronchiolitis (OB) in transplanted lungs. Many studies have tried to identify ideal candidate miRNAs and the downstream pathways implicated in the bronchiolar fibro-obliterative process. Several candidate miRNAs, previously indicated as possibly being associated with OB, were analyzed by combining the quantitative real time-polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH) of lung tissues of OB affected patients. Disease and OB-lesion-specific expression of miR-21-5p was confirmed and by computational analysis we were able to identify the network of genes most probably associated miR-21-5p in the context of OB fibrogenesis. Among all potentially associated genes, STAT3 had a very high probability score. Immunohistochemistry showed that STAT3/miR-21-5p were co-over expressed in OB lesions, thus, suggesting miR-21-5p could regulate STAT3 expression. However, miR-21-5p inhibition in cultures of bronchiolitis obliterans syndrome (BOS) derived myofibroblasts did not significantly affect STAT3 mRNA and protein expression levels. This study demonstrates the specificity of miR-21-5p over-expression in OB lesions and contributes to existing knowledge on the miR-21-5p downstream pathway. Activation of STAT3 is associated with miR-21-5p upregulation, however, STAT-3 network activation is most likely complex and miR-21-5p is not the sole regulator of STAT3. MDPI 2021-03-20 /pmc/articles/PMC8003603/ /pubmed/33804639 http://dx.doi.org/10.3390/cells10030688 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ). |
spellingShingle | Article Bozzini, Sara Pandolfi, Laura Rossi, Elena Inghilleri, Simona Zorzetto, Michele Ferrario, Giuseppina Di Carlo, Stefano Politano, Gianfranco De Silvestri, Annalisa Frangipane, Vanessa Porzio, Michele Kessler, Romain Calabrese, Fiorella Meloni, Federica Morbini, Patrizia miRNAs Potentially Involved in Post Lung Transplant-Obliterative Bronchiolitis: The Role of miR-21-5p |
title | miRNAs Potentially Involved in Post Lung Transplant-Obliterative Bronchiolitis: The Role of miR-21-5p |
title_full | miRNAs Potentially Involved in Post Lung Transplant-Obliterative Bronchiolitis: The Role of miR-21-5p |
title_fullStr | miRNAs Potentially Involved in Post Lung Transplant-Obliterative Bronchiolitis: The Role of miR-21-5p |
title_full_unstemmed | miRNAs Potentially Involved in Post Lung Transplant-Obliterative Bronchiolitis: The Role of miR-21-5p |
title_short | miRNAs Potentially Involved in Post Lung Transplant-Obliterative Bronchiolitis: The Role of miR-21-5p |
title_sort | mirnas potentially involved in post lung transplant-obliterative bronchiolitis: the role of mir-21-5p |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003603/ https://www.ncbi.nlm.nih.gov/pubmed/33804639 http://dx.doi.org/10.3390/cells10030688 |
work_keys_str_mv | AT bozzinisara mirnaspotentiallyinvolvedinpostlungtransplantobliterativebronchiolitistheroleofmir215p AT pandolfilaura mirnaspotentiallyinvolvedinpostlungtransplantobliterativebronchiolitistheroleofmir215p AT rossielena mirnaspotentiallyinvolvedinpostlungtransplantobliterativebronchiolitistheroleofmir215p AT inghillerisimona mirnaspotentiallyinvolvedinpostlungtransplantobliterativebronchiolitistheroleofmir215p AT zorzettomichele mirnaspotentiallyinvolvedinpostlungtransplantobliterativebronchiolitistheroleofmir215p AT ferrariogiuseppina mirnaspotentiallyinvolvedinpostlungtransplantobliterativebronchiolitistheroleofmir215p AT dicarlostefano mirnaspotentiallyinvolvedinpostlungtransplantobliterativebronchiolitistheroleofmir215p AT politanogianfranco mirnaspotentiallyinvolvedinpostlungtransplantobliterativebronchiolitistheroleofmir215p AT desilvestriannalisa mirnaspotentiallyinvolvedinpostlungtransplantobliterativebronchiolitistheroleofmir215p AT frangipanevanessa mirnaspotentiallyinvolvedinpostlungtransplantobliterativebronchiolitistheroleofmir215p AT porziomichele mirnaspotentiallyinvolvedinpostlungtransplantobliterativebronchiolitistheroleofmir215p AT kesslerromain mirnaspotentiallyinvolvedinpostlungtransplantobliterativebronchiolitistheroleofmir215p AT calabresefiorella mirnaspotentiallyinvolvedinpostlungtransplantobliterativebronchiolitistheroleofmir215p AT melonifederica mirnaspotentiallyinvolvedinpostlungtransplantobliterativebronchiolitistheroleofmir215p AT morbinipatrizia mirnaspotentiallyinvolvedinpostlungtransplantobliterativebronchiolitistheroleofmir215p |