{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T13:08:50Z","timestamp":1778504930684,"version":"3.51.4"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T00:00:00Z","timestamp":1638144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012021","name":"Iran University of Medical Sciences","doi-asserted-by":"publisher","award":["93-03-30-25094"],"award-info":[{"award-number":["93-03-30-25094"]}],"id":[{"id":"10.13039\/100012021","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Gender-related factors have explained the higher prevalence of autoimmune diseases in women. Sex hormones play a key role in the immune system and parenchymal cells function; therefore, these hormones can be important in the pathogenesis of autoimmune diseases as a risk or beneficial factor. Lung fibrosis is the main cause of mortality in systemic sclerosis, a female predominant autoimmune disease. The objective of this study was to examine the effect of progesterone on lung fibrosis in a mouse model of systemic sclerosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mice with bleomycin-induced lung fibrosis treated with progesterone subcutaneously for 21 and 28 days. Blood was collected for hormone and cytokine measurement at the end of treatment then, skin and lung tissues were harvested for histological assessment, gene expression, cytokine, hydroxyproline, and gelatinase measurement.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Trichrome staining and hydroxyproline measurements showed that progesterone treatment increased the content of collagen in fibrotic and normal lung tissues. Progesterone increased \u03b1-SMA (P &amp;lt; 0.01), TGF- \u03b2 (P &amp;lt; 0.05) and decreased MMP9 (P &amp;lt; 0.05) in fibrotic lung tissues. Also progesterone treatment decreased the gene expression of <jats:italic>Col1a2<\/jats:italic> (P &amp;lt;0.05), <jats:italic>Ctgf<\/jats:italic> (P &amp;lt;01), <jats:italic>End1<\/jats:italic> (0.001) in bleomycin- injured lung tissues. The serum level of TNF-\u03b1 was decreased, but the serum level of cortisol was increased by progesterone treatment in fibrotic mice (P&amp;lt; 0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results showed that progesterone aggravates lung fibrosis in a mouse model of systemic sclerosis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2021.742227","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T13:37:25Z","timestamp":1638365845000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Progesterone Aggravates Lung Fibrosis in a Mouse Model of Systemic Sclerosis"],"prefix":"10.3389","volume":"12","author":[{"given":"Fatemeh","family":"Vafashoar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazem","family":"Mousavizadeh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hadi","family":"Poormoghim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amir","family":"Haghighi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salar","family":"Pashangzadeh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nazanin","family":"Mojtabavi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032712-095937","article-title":"The Immunology of Fibrosis","volume":"31","author":"Wick","year":"2013","journal-title":"Annu Rev Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2019.00248","article-title":"Systemic Sclerosis Associated Interstitial Lung Disease: New Directions in Disease Management","volume":"6","author":"Barletta","year":"2019","journal-title":"Front Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"257","DOI":"10.2147\/CLEP.S191418","article-title":"Epidemiology of Systemic Sclerosis and Systemic Sclerosis-Associated Interstitial Lung Disease","volume":"11","author":"Bergamasco","year":"2019","journal-title":"Clin Epidemiol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.5301\/jsrd.5000209","article-title":"Gender Differences in Systemic Sclerosis: Relationship to Clinical Features, Serologic Status and Outcomes","volume":"1","author":"Peoples","year":"2016","journal-title":"J Scleroderma Relat Disord"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02279","article-title":"Sex Hormones in Acquired Immunity and Autoimmune Disease","volume":"9","author":"Moulton","year":"2018","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.18502\/ijaai.v18i1.635","article-title":"The Role of Progesterone in Cellular Apoptosis of Skin and Lung in a Bleomycin-Injured Mouse Model","volume":"18","author":"Vafashoar","year":"2019","journal-title":"Iran J Allergy Asthma Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.1999.00528.x","article-title":"Animal Model of Sclerotic Skin. 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