{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T04:40:52Z","timestamp":1769834452292,"version":"3.49.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"the Hospital Scientific research project of the First People\u2019s Hospital of Kashi","award":["KDYY202312"],"award-info":[{"award-number":["KDYY202312"]}]},{"name":"Kashi Regional Science and Technology Program Projects","award":["KS2023012"],"award-info":[{"award-number":["KS2023012"]}]},{"name":"Kashi Regional Science and Technology Program Projects","award":["KS2022033"],"award-info":[{"award-number":["KS2022033"]}]},{"name":"Dedicated funding for stem cell research project of the First People\u2019s Hospital of Kashi","award":["2023-13"],"award-info":[{"award-number":["2023-13"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-14286-4","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T21:30:55Z","timestamp":1754343055000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Pirfenidone combined with UC-MSCs reversed bleomycin-induced pulmonary fibrosis"],"prefix":"10.1038","volume":"15","author":[{"given":"Jingran","family":"Xu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zulipikaer","family":"Abudureheman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Gong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuemei","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lexin","family":"Xue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoguang","family":"Zou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,8,4]]},"reference":[{"key":"14286_CR1","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1001\/jama.2024.3669","volume":"331","author":"TM Maher","year":"2024","unstructured":"Maher, T. M. Interstitial lung disease: A review. JAMA 331, 1655\u20131665 (2024).","journal-title":"JAMA"},{"key":"14286_CR2","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.apsb.2021.07.023","volume":"12","author":"J Wang","year":"2022","unstructured":"Wang, J. et al. Targeting PI3K\/AKT signaling for treatment of idiopathic pulmonary fibrosis. Acta Pharm. Sin B. 12, 18\u201332 (2022).","journal-title":"Acta Pharm. Sin B"},{"key":"14286_CR3","doi-asserted-by":"publisher","first-page":"180076","DOI":"10.1183\/16000617.0076-2018","volume":"27","author":"V Cottin","year":"2018","unstructured":"Cottin, V. et al. Presentation, diagnosis and clinical course of the spectrum of progressive-fibrosing interstitial lung diseases. Eur Respir Rev 27, 180076 (2018).","journal-title":"Eur Respir Rev"},{"key":"14286_CR4","doi-asserted-by":"publisher","first-page":"107798","DOI":"10.1016\/j.pharmthera.2020.107798","volume":"222","author":"P Spagnolo","year":"2021","unstructured":"Spagnolo, P. et al. Idiopathic pulmonary fibrosis: disease mechanisms and drug development. Pharmacol. Ther. 222, 107798 (2021).","journal-title":"Pharmacol. Ther."},{"key":"14286_CR5","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1183\/09031936.00185114","volume":"46","author":"J Hutchinson","year":"2015","unstructured":"Hutchinson, J. et al. Global incidence and mortality of idiopathic pulmonary fibrosis: a systematic review. Eur. Respir J. 46, 795\u2013806 (2015).","journal-title":"Eur. Respir J."},{"key":"14286_CR6","doi-asserted-by":"publisher","first-page":"1941","DOI":"10.1016\/S0140-6736(17)30866-8","volume":"389","author":"L Richeldi","year":"2017","unstructured":"Richeldi, L. et al. Idiopathic pulmonary fibrosis. Lancet 389, 1941\u20131952 (2017).","journal-title":"Lancet"},{"key":"14286_CR7","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1186\/s12931-022-02192-6","volume":"23","author":"X Wu","year":"2022","unstructured":"Wu, X. et al. Human umbilical cord mesenchymal stem cells combined with Pirfenidone upregulates the expression of RGS2 in the pulmonary fibrosis in mice. Respir Res. 23, 270 (2022).","journal-title":"Respir Res."},{"key":"14286_CR8","doi-asserted-by":"publisher","first-page":"354","DOI":"10.4103\/1673-5374.317985","volume":"17","author":"G Wang","year":"2022","unstructured":"Wang, G. et al. Pre-clinical study of human umbilical cord mesenchymal stem cell transplantation for the treatment of traumatic brain injury: safety evaluation from Immunogenic and oncogenic perspectives. Neural Regen Res. 17, 354\u2013361 (2022).","journal-title":"Neural Regen Res."},{"key":"14286_CR9","first-page":"1065","volume":"37","author":"H Fikry","year":"2022","unstructured":"Fikry, H. et al. Therapeutic effect of adipose-derived mesenchymal stem cells (AD-MSCs) compared to Pirfenidone on corticosteroid resistance in a mouse model of acute exacerbation of idiopathic pulmonary fibrosis. Histol. Histopathol. 37, 1065\u20131083 (2022).","journal-title":"Histol. Histopathol"},{"key":"14286_CR10","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/s10753-019-01101-2","volume":"43","author":"ES Gad","year":"2020","unstructured":"Gad, E. S. et al. The Anti-fibrotic and Anti-inflammatory potential of bone Marrow-Derived mesenchymal stem cells and nintedanib in Bleomycin-Induced lung fibrosis in rats. Inflammation 43, 123\u2013134 (2020).","journal-title":"Inflammation"},{"key":"14286_CR11","doi-asserted-by":"publisher","first-page":"1701857","DOI":"10.1183\/13993003.01857-2017","volume":"52","author":"PS Bellaye","year":"2018","unstructured":"Bellaye, P. S. et al. Macitentan reduces progression of TGF-beta1-induced pulmonary fibrosis and pulmonary hypertension. Eur Respir J 52, 1701857 (2018).","journal-title":"Eur Respir J"},{"key":"14286_CR12","doi-asserted-by":"publisher","first-page":"2083","DOI":"10.1056\/NEJMoa1402582","volume":"370","author":"TE King Jr","year":"2014","unstructured":"King, T. E. Jr. et al. A phase 3 trial of Pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl. J. Med. 370, 2083\u20132092 (2014).","journal-title":"N Engl. J. Med."},{"key":"14286_CR13","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1016\/S2213-2600(20)30225-3","volume":"8","author":"PM George","year":"2020","unstructured":"George, P. M. et al. Pulmonary fibrosis and COVID-19: the potential role for antifibrotic therapy. Lancet Respir Med. 8, 807\u2013815 (2020).","journal-title":"Lancet Respir Med."},{"key":"14286_CR14","doi-asserted-by":"publisher","first-page":"1136761","DOI":"10.3389\/fphar.2023.1136761","volume":"14","author":"Y Yang","year":"2023","unstructured":"Yang, Y. et al. Mesenchymal stem cells and pulmonary fibrosis: a bibliometric and visualization analysis of literature published between 2002 and 2021. Front. Pharmacol. 14, 1136761 (2023).","journal-title":"Front. Pharmacol."},{"key":"14286_CR15","doi-asserted-by":"publisher","first-page":"L433","DOI":"10.1152\/ajplung.00128.2016","volume":"311","author":"S Aggarwal","year":"2016","unstructured":"Aggarwal, S. et al. Differential regulation of autophagy and mitophagy in pulmonary diseases. Am. J. Physiol. Lung Cell. Mol. Physiol. 311, L433\u2013452 (2016).","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"14286_CR16","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/S2213-2600(19)30341-8","volume":"8","author":"TM Maher","year":"2020","unstructured":"Maher, T. M. et al. Pirfenidone in patients with unclassifiable progressive fibrosing interstitial lung disease: a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Respir Med. 8, 147\u2013157 (2020).","journal-title":"Lancet Respir Med."},{"key":"14286_CR17","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.5966\/sctm.2015-0121","volume":"4","author":"N Srour","year":"2015","unstructured":"Srour, N. & Thebaud, B. Mesenchymal stromal cells in animal bleomycin pulmonary fibrosis models: A systematic review. Stem Cells Transl Med. 4, 1500\u20131510 (2015).","journal-title":"Stem Cells Transl Med."},{"key":"14286_CR18","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1002\/sctm.19-0037","volume":"9","author":"A Averyanov","year":"2020","unstructured":"Averyanov, A. et al. First-in-human high-cumulative-dose stem cell therapy in idiopathic pulmonary fibrosis with rapid lung function decline. Stem Cells Transl Med. 9, 6\u201316 (2020).","journal-title":"Stem Cells Transl Med."},{"key":"14286_CR19","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/j.chest.2016.10.061","volume":"151","author":"MK Glassberg","year":"2017","unstructured":"Glassberg, M. K. et al. Allogeneic human mesenchymal stem cells in patients with idiopathic pulmonary fibrosis via intravenous delivery (AETHER): A phase I safety clinical trial. Chest 151, 971\u2013981 (2017).","journal-title":"Chest"},{"key":"14286_CR20","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1165\/rcmb.2018-0083ED","volume":"59","author":"CJ Le Saux","year":"2018","unstructured":"Le Saux, C. J. & Chapman, H. A. Idiopathic pulmonary fibrosis: cell death and inflammation revisited. Am. J. Respir Cell. Mol. Biol. 59, 137\u2013138 (2018).","journal-title":"Am. J. Respir Cell. Mol. Biol."},{"key":"14286_CR21","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1038\/s41418-020-00650-6","volume":"28","author":"LZ Rao","year":"2021","unstructured":"Rao, L. Z. et al. IL-24 deficiency protects mice against bleomycin-induced pulmonary fibrosis by repressing IL-4-induced M2 program in macrophages. Cell. Death Differ. 28, 1270\u20131283 (2021).","journal-title":"Cell. Death Differ."},{"key":"14286_CR22","doi-asserted-by":"publisher","first-page":"L925","DOI":"10.1152\/ajplung.00582.2020","volume":"321","author":"S Senoo","year":"2021","unstructured":"Senoo, S. et al. Essential role of IL-23 in the development of acute exacerbation of pulmonary fibrosis. Am. J. Physiol. Lung Cell. Mol. Physiol. 321, L925\u2013L940 (2021).","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"14286_CR23","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1186\/s13287-019-1365-z","volume":"10","author":"JD Silva","year":"2019","unstructured":"Silva, J. D. et al. Eicosapentaenoic acid potentiates the therapeutic effects of adipose tissue-derived mesenchymal stromal cells on lung and distal organ injury in experimental sepsis. Stem Cell. Res. Ther. 10, 264 (2019).","journal-title":"Stem Cell. Res. Ther."},{"key":"14286_CR24","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1002\/sctm.18-0042","volume":"7","author":"A Navas","year":"2018","unstructured":"Navas, A. et al. Anti-Inflammatory and Anti-Fibrotic effects of human amniotic membrane mesenchymal stem cells and their potential in corneal repair. Stem Cells Transl Med. 7, 906\u2013917 (2018).","journal-title":"Stem Cells Transl Med."},{"key":"14286_CR25","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.rmed.2018.12.015","volume":"147","author":"P Heukels","year":"2019","unstructured":"Heukels, P. et al. Inflammation and immunity in IPF pathogenesis and treatment. Respir Med. 147, 79\u201391 (2019).","journal-title":"Respir Med."},{"key":"14286_CR26","doi-asserted-by":"publisher","first-page":"192","DOI":"10.15283\/ijsc16041","volume":"9","author":"M Reddy","year":"2016","unstructured":"Reddy, M. et al. Human Adipose-derived mesenchymal stem cells attenuate early stage of bleomycin induced pulmonary fibrosis: comparison with Pirfenidone. Int. J. Stem Cells. 9, 192\u2013206 (2016).","journal-title":"Int. J. Stem Cells"},{"key":"14286_CR27","doi-asserted-by":"publisher","first-page":"114172","DOI":"10.1016\/j.bcp.2020.114172","volume":"180","author":"Y Huang","year":"2020","unstructured":"Huang, Y. et al. TGF-beta1-induced miR-424 promotes pulmonary myofibroblast differentiation by targeting Slit2 protein expression. Biochem. Pharmacol. 180, 114172 (2020).","journal-title":"Biochem. Pharmacol."},{"key":"14286_CR28","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/s12890-018-0626-4","volume":"18","author":"M Molina-Molina","year":"2018","unstructured":"Molina-Molina, M. et al. Anti-fibrotic effects of Pirfenidone and Rapamycin in primary IPF fibroblasts and human alveolar epithelial cells. BMC Pulm Med. 18, 63 (2018).","journal-title":"BMC Pulm Med."},{"key":"14286_CR29","doi-asserted-by":"publisher","first-page":"797292","DOI":"10.3389\/fphar.2021.797292","volume":"12","author":"Q Mei","year":"2021","unstructured":"Mei, Q. et al. Idiopathic pulmonary fibrosis: an update on pathogenesis. Front. Pharmacol. 12, 797292 (2021).","journal-title":"Front. Pharmacol."},{"key":"14286_CR30","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1165\/rcmb.2017-0248OC","volume":"60","author":"SH Lacy","year":"2019","unstructured":"Lacy, S. H. et al. Activated human lung fibroblasts produce extracellular vesicles with antifibrotic prostaglandins. Am. J. Respir Cell. Mol. Biol. 60, 269\u2013278 (2019).","journal-title":"Am. J. Respir Cell. Mol. Biol."},{"key":"14286_CR31","doi-asserted-by":"publisher","first-page":"381","DOI":"10.3390\/pharmaceutics14020381","volume":"14","author":"R Alvites","year":"2022","unstructured":"Alvites, R. et al. Mesenchymal stem\/stromal cells and their paracrine Activity-Immunomodulation mechanisms and how to influence the therapeutic potential. Pharmaceutics 14, 381 (2022).","journal-title":"Pharmaceutics"},{"key":"14286_CR32","doi-asserted-by":"publisher","first-page":"7819","DOI":"10.1111\/jcmm.14661","volume":"23","author":"W Zhang","year":"2019","unstructured":"Zhang, W. et al. Schistosoma Japonicum peptide SJMHE1 suppresses airway inflammation of allergic asthma in mice. J. Cell. Mol. Med. 23, 7819\u20137829 (2019).","journal-title":"J. Cell. Mol. Med."},{"key":"14286_CR33","doi-asserted-by":"publisher","first-page":"e0196048","DOI":"10.1371\/journal.pone.0196048","volume":"13","author":"G Moroncini","year":"2018","unstructured":"Moroncini, G. et al. Mesenchymal stromal cells from human umbilical cord prevent the development of lung fibrosis in immunocompetent mice. PLoS One. 13, e0196048 (2018).","journal-title":"PLoS One"},{"key":"14286_CR34","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s13287-020-02072-0","volume":"12","author":"L Dong","year":"2021","unstructured":"Dong, L. et al. Hypoxic hUCMSC-derived extracellular vesicles attenuate allergic airway inflammation and airway remodeling in chronic asthma mice. Stem Cell. Res. Ther. 12, 4 (2021).","journal-title":"Stem Cell. Res. Ther."},{"key":"14286_CR35","doi-asserted-by":"publisher","first-page":"5244","DOI":"10.3390\/ijms25105244","volume":"25","author":"T Akter","year":"2024","unstructured":"Akter, T. et al. IQGAP1 regulates actin polymerization and contributes to Bleomycin-Induced lung fibrosis. Int J. Mol. Sci 25, 5244 (2024).","journal-title":"Int J. Mol. Sci"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-14286-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-14286-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-14286-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T16:15:49Z","timestamp":1757348149000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-14286-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,4]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["14286"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-14286-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,4]]},"assertion":[{"value":"10 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 July 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 August 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"All animal experiments were approved by the Ethics Committee of Xinjiang Medical University (IACUC-20231010-06). This study was conducted in accordance with relevant guidelines and regulations.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}],"article-number":"28339"}}