Sex-Related Differences in Murine Models of Chemically Induced Pulmonary Fibrosis
We developed two models of chemically induced chronic lung injury and pulmonary fibrosis in mice (intratracheally administered hydrochloric acid (HCl) and intratracheally administered nitrogen mustard (NM)) and investigated male–female differences. Female mice exhibited higher 30-day survival and le...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/11/5909 |
| _version_ | 1797531878790529024 |
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| author | Pavel Solopov Ruben Manuel Luciano Colunga Biancatelli Christiana Dimitropoulou John D. Catravas |
| author_facet | Pavel Solopov Ruben Manuel Luciano Colunga Biancatelli Christiana Dimitropoulou John D. Catravas |
| author_sort | Pavel Solopov |
| collection | DOAJ |
| description | We developed two models of chemically induced chronic lung injury and pulmonary fibrosis in mice (intratracheally administered hydrochloric acid (HCl) and intratracheally administered nitrogen mustard (NM)) and investigated male–female differences. Female mice exhibited higher 30-day survival and less weight loss than male mice. Thirty days after the instillation of either HCl or NM, bronchoalveolar lavage fluid displayed a persistent, mild inflammatory response, but with higher white blood cell numbers and total protein content in males vs. females. Furthermore, females exhibited less collagen deposition, milder pulmonary fibrosis, and lower Ashcroft scores. After instillation of either HCl or NM, all animals displayed increased values of phosphorylated (activated) Heat Shock Protein 90, which plays a crucial role in the alveolar wound-healing processes; however, females presented lower activation of both transforming growth factor-β (TGF-β) signaling pathways: ERK and SMAD. We propose that female mice are protected from chronic complications of a single exposure to either HCl or NM through a lesser activation of TGF-β and downstream signaling. The understanding of the molecular mechanisms that confer a protective effect in females could help develop new, gender-specific therapeutics for IPF. |
| first_indexed | 2024-03-10T10:51:03Z |
| format | Article |
| id | doaj.art-bc2197213fef448fae9d4b5c3beb8dc0 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T10:51:03Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-bc2197213fef448fae9d4b5c3beb8dc02023-11-21T22:14:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-012211590910.3390/ijms22115909Sex-Related Differences in Murine Models of Chemically Induced Pulmonary FibrosisPavel Solopov0Ruben Manuel Luciano Colunga Biancatelli1Christiana Dimitropoulou2John D. Catravas3Frank Reidy Research Center for Bioelectrics Old Dominion University, Norfolk, VA 23508, USAFrank Reidy Research Center for Bioelectrics Old Dominion University, Norfolk, VA 23508, USAFrank Reidy Research Center for Bioelectrics Old Dominion University, Norfolk, VA 23508, USAFrank Reidy Research Center for Bioelectrics Old Dominion University, Norfolk, VA 23508, USAWe developed two models of chemically induced chronic lung injury and pulmonary fibrosis in mice (intratracheally administered hydrochloric acid (HCl) and intratracheally administered nitrogen mustard (NM)) and investigated male–female differences. Female mice exhibited higher 30-day survival and less weight loss than male mice. Thirty days after the instillation of either HCl or NM, bronchoalveolar lavage fluid displayed a persistent, mild inflammatory response, but with higher white blood cell numbers and total protein content in males vs. females. Furthermore, females exhibited less collagen deposition, milder pulmonary fibrosis, and lower Ashcroft scores. After instillation of either HCl or NM, all animals displayed increased values of phosphorylated (activated) Heat Shock Protein 90, which plays a crucial role in the alveolar wound-healing processes; however, females presented lower activation of both transforming growth factor-β (TGF-β) signaling pathways: ERK and SMAD. We propose that female mice are protected from chronic complications of a single exposure to either HCl or NM through a lesser activation of TGF-β and downstream signaling. The understanding of the molecular mechanisms that confer a protective effect in females could help develop new, gender-specific therapeutics for IPF.https://www.mdpi.com/1422-0067/22/11/5909idiopathic pulmonary fibrosis (IPF)nitrogen mustardhydrochloric acidgender differencesheat shock proteinsfibrosis |
| spellingShingle | Pavel Solopov Ruben Manuel Luciano Colunga Biancatelli Christiana Dimitropoulou John D. Catravas Sex-Related Differences in Murine Models of Chemically Induced Pulmonary Fibrosis International Journal of Molecular Sciences idiopathic pulmonary fibrosis (IPF) nitrogen mustard hydrochloric acid gender differences heat shock proteins fibrosis |
| title | Sex-Related Differences in Murine Models of Chemically Induced Pulmonary Fibrosis |
| title_full | Sex-Related Differences in Murine Models of Chemically Induced Pulmonary Fibrosis |
| title_fullStr | Sex-Related Differences in Murine Models of Chemically Induced Pulmonary Fibrosis |
| title_full_unstemmed | Sex-Related Differences in Murine Models of Chemically Induced Pulmonary Fibrosis |
| title_short | Sex-Related Differences in Murine Models of Chemically Induced Pulmonary Fibrosis |
| title_sort | sex related differences in murine models of chemically induced pulmonary fibrosis |
| topic | idiopathic pulmonary fibrosis (IPF) nitrogen mustard hydrochloric acid gender differences heat shock proteins fibrosis |
| url | https://www.mdpi.com/1422-0067/22/11/5909 |
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