Simple gene signature to assess murine fibroblast polarization
Abstract We provide an original multi-stage approach identifying a gene signature to assess murine fibroblast polarization. Prototypic polarizations (inflammatory/fibrotic) were induced by seeded mouse embryonic fibroblasts (MEFs) with TNFα or TGFß1, respectively. The transcriptomic and proteomic pr...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-15640-6 |
| _version_ | 1811293694503944192 |
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| author | Emmanuel Ledoult Manel Jendoubi Aurore Collet Thomas Guerrier Alexis Largy Silvia Speca Solange Vivier Fabrice Bray Martin Figeac Eric Hachulla Myriam Labalette Frédéric Leprêtre Shéhérazade Sebda Sébastien Sanges Christian Rolando Vincent Sobanski Sylvain Dubucquoi David Launay |
| author_facet | Emmanuel Ledoult Manel Jendoubi Aurore Collet Thomas Guerrier Alexis Largy Silvia Speca Solange Vivier Fabrice Bray Martin Figeac Eric Hachulla Myriam Labalette Frédéric Leprêtre Shéhérazade Sebda Sébastien Sanges Christian Rolando Vincent Sobanski Sylvain Dubucquoi David Launay |
| author_sort | Emmanuel Ledoult |
| collection | DOAJ |
| description | Abstract We provide an original multi-stage approach identifying a gene signature to assess murine fibroblast polarization. Prototypic polarizations (inflammatory/fibrotic) were induced by seeded mouse embryonic fibroblasts (MEFs) with TNFα or TGFß1, respectively. The transcriptomic and proteomic profiles were obtained by RNA microarray and LC-MS/MS. Gene Ontology and pathways analysis were performed among the differentially expressed genes (DEGs) and proteins (DEPs). Balb/c mice underwent daily intradermal injections of HOCl (or PBS) as an experimental murine model of inflammation-mediated fibrosis in a time-dependent manner. As results, 1456 and 2215 DEGs, and 289 and 233 DEPs were respectively found in MEFs in response to TNFα or TGFß1, respectively. Among the most significant pathways, we combined 26 representative genes to encompass the proinflammatory and profibrotic polarizations of fibroblasts. Based on principal component analysis, this signature deciphered baseline state, proinflammatory polarization, and profibrotic polarization as accurately as RNA microarray and LC-MS/MS did. Then, we assessed the gene signature on dermal fibroblasts isolated from the experimental murine model. We observed a proinflammatory polarization at day 7, and a mixture of a proinflammatory and profibrotic polarizations at day 42 in line with histological findings. Our approach provides a small-size and convenient gene signature to assess murine fibroblast polarization. |
| first_indexed | 2024-04-13T05:05:14Z |
| format | Article |
| id | doaj.art-3b929e9e55f1469f8ebd0f605909aaa3 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T05:05:14Z |
| publishDate | 2022-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-3b929e9e55f1469f8ebd0f605909aaa32022-12-22T03:01:11ZengNature PortfolioScientific Reports2045-23222022-07-0112111310.1038/s41598-022-15640-6Simple gene signature to assess murine fibroblast polarizationEmmanuel Ledoult0Manel Jendoubi1Aurore Collet2Thomas Guerrier3Alexis Largy4Silvia Speca5Solange Vivier6Fabrice Bray7Martin Figeac8Eric Hachulla9Myriam Labalette10Frédéric Leprêtre11Shéhérazade Sebda12Sébastien Sanges13Christian Rolando14Vincent Sobanski15Sylvain Dubucquoi16David Launay17Inserm, U1286Inserm, U1286Inserm, U1286Inserm, U1286INFINITE - Institute for Translational Research in Inflammation, Univ. LilleInserm, U1286Inserm, U1286CNRS, UAR 3290 - MSAP - Miniaturisation Pour La Synthèse, Univ. LilleCNRS, Inserm, CHU Lille, Institut Pasteur de Lille, US 41 - UMS 2014 - PLBS, Univ. LilleInserm, U1286Inserm, U1286CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, US 41 - UMS 2014 - PLBS, Univ. LilleCNRS, Inserm, CHU Lille, Institut Pasteur de Lille, US 41 - UMS 2014 - PLBS, Univ. LilleInserm, U1286CNRS, UAR 3290 - MSAP - Miniaturisation Pour La Synthèse, Univ. LilleInserm, U1286Inserm, U1286Inserm, U1286Abstract We provide an original multi-stage approach identifying a gene signature to assess murine fibroblast polarization. Prototypic polarizations (inflammatory/fibrotic) were induced by seeded mouse embryonic fibroblasts (MEFs) with TNFα or TGFß1, respectively. The transcriptomic and proteomic profiles were obtained by RNA microarray and LC-MS/MS. Gene Ontology and pathways analysis were performed among the differentially expressed genes (DEGs) and proteins (DEPs). Balb/c mice underwent daily intradermal injections of HOCl (or PBS) as an experimental murine model of inflammation-mediated fibrosis in a time-dependent manner. As results, 1456 and 2215 DEGs, and 289 and 233 DEPs were respectively found in MEFs in response to TNFα or TGFß1, respectively. Among the most significant pathways, we combined 26 representative genes to encompass the proinflammatory and profibrotic polarizations of fibroblasts. Based on principal component analysis, this signature deciphered baseline state, proinflammatory polarization, and profibrotic polarization as accurately as RNA microarray and LC-MS/MS did. Then, we assessed the gene signature on dermal fibroblasts isolated from the experimental murine model. We observed a proinflammatory polarization at day 7, and a mixture of a proinflammatory and profibrotic polarizations at day 42 in line with histological findings. Our approach provides a small-size and convenient gene signature to assess murine fibroblast polarization.https://doi.org/10.1038/s41598-022-15640-6 |
| spellingShingle | Emmanuel Ledoult Manel Jendoubi Aurore Collet Thomas Guerrier Alexis Largy Silvia Speca Solange Vivier Fabrice Bray Martin Figeac Eric Hachulla Myriam Labalette Frédéric Leprêtre Shéhérazade Sebda Sébastien Sanges Christian Rolando Vincent Sobanski Sylvain Dubucquoi David Launay Simple gene signature to assess murine fibroblast polarization Scientific Reports |
| title | Simple gene signature to assess murine fibroblast polarization |
| title_full | Simple gene signature to assess murine fibroblast polarization |
| title_fullStr | Simple gene signature to assess murine fibroblast polarization |
| title_full_unstemmed | Simple gene signature to assess murine fibroblast polarization |
| title_short | Simple gene signature to assess murine fibroblast polarization |
| title_sort | simple gene signature to assess murine fibroblast polarization |
| url | https://doi.org/10.1038/s41598-022-15640-6 |
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