The role of eCIRP in bleomycin-induced pulmonary fibrosis in mice.
<h4>Objective and design</h4>We examined the role of eCIRP in the pathogenesis of bleomycin-induced pulmonary fibrosis (PF).<h4>Material and methods</h4>Publicly available gene expression omnibus datasets were analyzed for the expression of CIRP in lung samples from patients...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0266163 |
| _version_ | 1818239310507278336 |
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| author | Siavash Bolourani Ezgi Sari Max Brenner Ping Wang |
| author_facet | Siavash Bolourani Ezgi Sari Max Brenner Ping Wang |
| author_sort | Siavash Bolourani |
| collection | DOAJ |
| description | <h4>Objective and design</h4>We examined the role of eCIRP in the pathogenesis of bleomycin-induced pulmonary fibrosis (PF).<h4>Material and methods</h4>Publicly available gene expression omnibus datasets were analyzed for the expression of CIRP in lung samples from patients with PF. Wild type (WT) or CIRP-/- mice received daily injections of 10 μg/g bleomycin for 10 days. A subset of bleomycin-injected WT mice was treated with the eCIRP antagonist C23 (8 μg/g/day) from day 10 to day 19. At three weeks, transthoracic echocardiography was performed to measure the degree of pulmonary hypertension, and lung tissues were collected and analyzed for markers of fibrosis.<h4>Results</h4>Analysis of the mRNA data of human lung samples showed a significant positive correlation between CIRP and α-smooth muscle actin (α-SMA), an important marker of fibrosis. Moreover, the expression of CIRP was higher in patients with acute exacerbation of PF than in patients with stable PF. CIRP-/- mice showed attenuated induction of α-SMA and collagens (Col1a1, Col3a1), reduced hydroxyproline content, decreased histological fibrosis scores, and improved pulmonary hypertension as compared to WT mice. WT mice treated with C23 also had significant attenuation of the above endpoint measure.<h4>Conclusions</h4>Our study demonstrates that eCIRP plays a key role in promoting the development of PF, and blocking eCIRP with C23 can significantly attenuate this process. |
| first_indexed | 2024-12-12T12:55:31Z |
| format | Article |
| id | doaj.art-a20aac2ee5c34d7399514bc8003ca677 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T12:55:31Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-a20aac2ee5c34d7399514bc8003ca6772022-12-22T00:23:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01174e026616310.1371/journal.pone.0266163The role of eCIRP in bleomycin-induced pulmonary fibrosis in mice.Siavash BolouraniEzgi SariMax BrennerPing Wang<h4>Objective and design</h4>We examined the role of eCIRP in the pathogenesis of bleomycin-induced pulmonary fibrosis (PF).<h4>Material and methods</h4>Publicly available gene expression omnibus datasets were analyzed for the expression of CIRP in lung samples from patients with PF. Wild type (WT) or CIRP-/- mice received daily injections of 10 μg/g bleomycin for 10 days. A subset of bleomycin-injected WT mice was treated with the eCIRP antagonist C23 (8 μg/g/day) from day 10 to day 19. At three weeks, transthoracic echocardiography was performed to measure the degree of pulmonary hypertension, and lung tissues were collected and analyzed for markers of fibrosis.<h4>Results</h4>Analysis of the mRNA data of human lung samples showed a significant positive correlation between CIRP and α-smooth muscle actin (α-SMA), an important marker of fibrosis. Moreover, the expression of CIRP was higher in patients with acute exacerbation of PF than in patients with stable PF. CIRP-/- mice showed attenuated induction of α-SMA and collagens (Col1a1, Col3a1), reduced hydroxyproline content, decreased histological fibrosis scores, and improved pulmonary hypertension as compared to WT mice. WT mice treated with C23 also had significant attenuation of the above endpoint measure.<h4>Conclusions</h4>Our study demonstrates that eCIRP plays a key role in promoting the development of PF, and blocking eCIRP with C23 can significantly attenuate this process.https://doi.org/10.1371/journal.pone.0266163 |
| spellingShingle | Siavash Bolourani Ezgi Sari Max Brenner Ping Wang The role of eCIRP in bleomycin-induced pulmonary fibrosis in mice. PLoS ONE |
| title | The role of eCIRP in bleomycin-induced pulmonary fibrosis in mice. |
| title_full | The role of eCIRP in bleomycin-induced pulmonary fibrosis in mice. |
| title_fullStr | The role of eCIRP in bleomycin-induced pulmonary fibrosis in mice. |
| title_full_unstemmed | The role of eCIRP in bleomycin-induced pulmonary fibrosis in mice. |
| title_short | The role of eCIRP in bleomycin-induced pulmonary fibrosis in mice. |
| title_sort | role of ecirp in bleomycin induced pulmonary fibrosis in mice |
| url | https://doi.org/10.1371/journal.pone.0266163 |
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