{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:18Z","timestamp":1787028558785,"version":"build-2736575974"},"reference-count":75,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T00:00:00Z","timestamp":1742169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Science and Technology in Theranostics and Biotechnology","award":["403193\/2022-2"],"award-info":[{"award-number":["403193\/2022-2"]}]},{"name":"National Institutes of Science and Technology in Theranostics and Biotechnology","award":["CBB-APQ-03613-17"],"award-info":[{"award-number":["CBB-APQ-03613-17"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Idiopathic pulmonary fibrosis (IPF) is a progressive and incurable chronic interstitial lung disease characterized by excessive fibrosis and impaired lung function. Current treatments, such as pirfenidone and nintedanib, slow disease progression but fail to halt or reverse fibrosis, highlighting the need for novel approaches. Activin A, which belongs to the TGF-\u03b2 superfamily, is implicated in various fibrosis-related mechanisms, including epithelial\u2013mesenchymal transition (EMT), a process where epithelial cells acquire mesenchymal characteristics, and fibroblast\u2013myofibroblast transformation (FMT), in which fibroblasts differentiate into contractile myofibroblasts. It also promotes inflammatory cytokine release and extracellular matrix buildup. This study aimed to inhibit Activin A activity using synthetic peptides identified through phage display screening. Of the ten peptides isolated, A7, B9, and E10 demonstrated high binding affinity and inhibitory activity. Computational modeling confirmed that these peptides target the receptor-binding domain of Activin A, with peptide E10 exhibiting superior efficacy. Functional assays showed that E10 reduced cell migration, inhibited EMT in A549 cells, and suppressed FMT in fibroblast cultures, even under pro-fibrotic stimulation with TGF-\u03b2. These findings underscore the therapeutic potential of targeting Activin A with synthetic peptides, offering a promising avenue for IPF treatment and expanding the arsenal of anti-fibrotic strategies.<\/jats:p>","DOI":"10.3390\/ijms26062705","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T15:24:56Z","timestamp":1742225096000},"page":"2705","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Activin A Inhibitory Peptides Suppress Fibrotic Pathways by Targeting Epithelial\u2013Mesenchymal Transition and Fibroblast\u2013Myofibroblast Transformation in Idiopathic Pulmonary Fibrosis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1953-6318","authenticated-orcid":false,"given":"Victor Alexandre F.","family":"Bastos","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Biotechnology, Institute of Biotechnology, Federal University of Uberl\u00e2ndia, Uberl\u00e2ndia 38402-022, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia Tiemi","family":"Fujimura","sequence":"additional","affiliation":[{"name":"Laboratory of Nanobiotechnology\u2014Prof. Dr. Luiz Ricardo Goulart Filho, Institute of Biotechnology, Federal University of Uberl\u00e2ndia, Uberl\u00e2ndia 38402-022, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline Gomes de","family":"Souza","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging, Hematology, and Oncology, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, Ribeirao Preto 14040-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Em\u00edlia Rezende","family":"Vaz","sequence":"additional","affiliation":[{"name":"Laboratory of Nanobiotechnology\u2014Prof. Dr. Luiz Ricardo Goulart Filho, Institute of Biotechnology, Federal University of Uberl\u00e2ndia, Uberl\u00e2ndia 38402-022, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1180-5408","authenticated-orcid":false,"given":"Natieli","family":"Saito","sequence":"additional","affiliation":[{"name":"Laboratory of Nanobiotechnology\u2014Prof. Dr. Luiz Ricardo Goulart Filho, Institute of Biotechnology, Federal University of Uberl\u00e2ndia, Uberl\u00e2ndia 38402-022, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2104-5780","authenticated-orcid":false,"given":"Robinson","family":"Sabino-Silva","sequence":"additional","affiliation":[{"name":"Department of Physiology, Laboratory of Nanobiotechnology\u2014Prof. Dr. Luiz Ricardo Goulart Filho, Innovation Center in Salivary Diagnostics and Nanobiotechnology, Institute of Biomedical Sciences, Federal University of Uberl\u00e2ndia, Uberl\u00e2ndia 38402-022, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1803-4861","authenticated-orcid":false,"given":"Luiz Ricardo","family":"Goulart","sequence":"additional","affiliation":[{"name":"Laboratory of Nanobiotechnology\u2014Prof. Dr. Luiz Ricardo Goulart Filho, Institute of Biotechnology, Federal University of Uberl\u00e2ndia, Uberl\u00e2ndia 38402-022, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2707-757X","authenticated-orcid":false,"given":"Thulio Marquez","family":"Cunha","sequence":"additional","affiliation":[{"name":"Laboratory of Nanobiotechnology\u2014Prof. Dr. Luiz Ricardo Goulart Filho, Institute of Biotechnology, Federal University of Uberl\u00e2ndia, Uberl\u00e2ndia 38402-022, MG, Brazil"},{"name":"School of Medicine, Federal University of Uberl\u00e2ndia, Uberl\u00e2ndia 38408-100, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,17]]},"reference":[{"key":"ref_1","first-page":"227","article-title":"Idiopathic Pulmonary Fibrosis","volume":"64","author":"Urteaga","year":"2022","journal-title":"Radiol. (Engl. Ed.)"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"107798","DOI":"10.1016\/j.pharmthera.2020.107798","article-title":"Idiopathic Pulmonary Fibrosis: Disease Mechanisms and Drug Development","volume":"222","author":"Spagnolo","year":"2021","journal-title":"Pharmacol. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/S2213-2600(20)30355-6","article-title":"Progressive Fibrosing Interstitial Lung Disease: Clinical Uncertainties, Consensus Recommendations, and Research Priorities","volume":"8","author":"George","year":"2020","journal-title":"Lancet Respir. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"104166","DOI":"10.1016\/j.lpm.2023.104166","article-title":"Idiopathic Pulmonary Fibrosis","volume":"52","author":"Koudstaal","year":"2023","journal-title":"Presse Medicale"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1111\/crj.13466","article-title":"Idiopathic Pulmonary Fibrosis: Current and Future Treatment","volume":"16","author":"Glass","year":"2022","journal-title":"Clin. Respir. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2200957","DOI":"10.1183\/13993003.00957-2022","article-title":"Idiopathic Pulmonary Fibrosis: State of the Art for 2023","volume":"61","author":"Podolanczuk","year":"2022","journal-title":"Eur. Respir. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"102261","DOI":"10.1016\/j.pupt.2023.102261","article-title":"The Impact of Nintedanib and Pirfenidone on Lung Function and Survival in Patients with Idiopathic Pulmonary Fibrosis in Real-Life Setting","volume":"83","author":"Santos","year":"2023","journal-title":"Pulm. Pharmacol. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e29266","DOI":"10.1016\/j.heliyon.2024.e29266","article-title":"Bibliometric Analysis of the Pirfenidone and Nintedanib in Interstitial Lung Diseases","volume":"10","author":"Liu","year":"2024","journal-title":"Heliyon"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"102314","DOI":"10.1016\/j.jaut.2019.102314","article-title":"Activin-A in the Regulation of Immunity in Health and Disease","volume":"104","author":"Morianos","year":"2019","journal-title":"J. Autoimmun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7709","DOI":"10.21037\/jtd-24-680","article-title":"Exacerbation of Pulmonary Fibrosis Following Acute Lung Injury via Activin-A Production by Recruited Alveolar Macrophages","volume":"16","author":"Pan","year":"2024","journal-title":"J. Thorac. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.jaci.2005.09.017","article-title":"Activin A Is an Acute Allergen-Responsive Cytokine and Provides a Link to TGF-\u03b2\u2013Mediated Airway Remodeling in Asthma","volume":"117","author":"Karagiannidis","year":"2006","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"112709","DOI":"10.1016\/j.intimp.2024.112709","article-title":"Pathological Insights into Activin A: Molecular Underpinnings and Therapeutic Prospects in Various Diseases","volume":"139","author":"Kundra","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.mce.2004.07.010","article-title":"Activin A and Follistatin in Systemic Inflammation","volume":"225","author":"Jones","year":"2004","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1007\/s00408-021-00470-6","article-title":"Progranulin and Activin A Concentrations Are Elevated in Serum from Patients with Acute Exacerbations of Idiopathic Pulmonary Fibrosis","volume":"199","author":"Xie","year":"2021","journal-title":"Lung"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s12964-019-0361-3","article-title":"Activin a Promotes Myofibroblast Differentiation of Endometrial Mesenchymal Stem Cells via STAT3-Dependent Smad\/CTGF Pathway","volume":"17","author":"Zhang","year":"2019","journal-title":"Cell Commun. Signal."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1038\/s41580-024-00716-0","article-title":"Fibroblast and Myofibroblast Activation in Normal Tissue Repair and Fibrosis","volume":"25","author":"Younesi","year":"2024","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1038\/icb.2015.7","article-title":"The Activin A Antagonist Follistatin Inhibits Cystic Fibrosis-like Lung Inflammation and Pathology","volume":"93","author":"Hardy","year":"2015","journal-title":"Immunol. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2604","DOI":"10.1038\/s41467-020-16409-z","article-title":"Activin-Mediated Alterations of the Fibroblast Transcriptome and Matrisome Control the Biomechanical Properties of Skin Wounds","volume":"11","author":"Wietecha","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cytogfr.2024.11.004","article-title":"The Activin-Follistatin System: Key Regulator of Kidney Development, Regeneration, Inflammation, and Fibrosis","volume":"81","author":"Nagayama","year":"2024","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1038\/sj.emboj.7601000","article-title":"Structural Basis for the Inhibition of Activin Signalling by Follistatin","volume":"25","author":"Harrington","year":"2006","journal-title":"EMBO J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1126\/science.abb0993","article-title":"A Phosphorylation-Regulated EIF3d Translation Switch Mediates Cellular Adaptation to Metabolic Stress","volume":"370","author":"Lamper","year":"2020","journal-title":"Science"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4916","DOI":"10.1021\/acsbiomaterials.4c00736","article-title":"Quantifying and Controlling the Proteolytic Degradation of Cell Adhesion Peptides","volume":"10","author":"Rozans","year":"2024","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Rozans, S.J., Moghaddam, A.S., and Pashuck, E.T. (2024). A Streamlined High-Throughput LC-MS Assay for Quantifying Peptide Degradation in Cell Culture. bioRxiv, 113.","DOI":"10.1101\/2024.10.11.617883"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1007\/s40265-023-01950-0","article-title":"Current and Future Treatment Landscape for Idiopathic Pulmonary Fibrosis","volume":"83","author":"Bonella","year":"2023","journal-title":"Drugs"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Guo, H., Sun, J., Zhang, S., Nie, Y., Zhou, S., and Zeng, Y. (2023). Progress in Understanding and Treating Idiopathic Pulmonary Fibrosis: Recent Insights and Emerging Therapies. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1205948"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Chianese, M., Screm, G., Salton, F., Confalonieri, P., Trotta, L., Barbieri, M., Ruggero, L., Mari, M., Reccardini, N., and Geri, P. (2024). Pirfenidone and Nintedanib in Pulmonary Fibrosis: Lights and Shadows. Pharmaceuticals, 17.","DOI":"10.3390\/ph17060709"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1007\/s00228-024-03720-7","article-title":"Real-World Safety and Effectiveness of Pirfenidone and Nintedanib in the Treatment of Idiopathic Pulmonary Fibrosis: A Systematic Review and Meta-Analysis","volume":"80","author":"Kou","year":"2024","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1208\/s12249-024-02793-y","article-title":"Revolutionizing the Treatment of Idiopathic Pulmonary Fibrosis: From Conventional Therapies to Advanced Drug Delivery Systems","volume":"25","author":"Singh","year":"2024","journal-title":"AAPS PharmSciTech"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.arbr.2019.05.012","article-title":"The Future of Pharmacological Treatment in Idiopathic Pulmonary Fibrosis","volume":"55","year":"2019","journal-title":"Arch. Bronconeumol. (Engl. Ed.)"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Libra, A., Sciacca, E., Muscato, G., Sambataro, G., Spicuzza, L., and Vancheri, C. (2024). Highlights on Future Treatments of IPF: Clues and Pitfalls. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25158392"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"100167","DOI":"10.1016\/j.medidd.2023.100167","article-title":"Idiopathic Pulmonary Fibrosis: Pathophysiology, Cellular Signaling, Diagnostic and Therapeutic Approaches","volume":"20","author":"Shakeel","year":"2023","journal-title":"Accel. Drug Discov."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Namwanje, M., and Brown, C.W. (2016). Activins and Inhibins: Roles in Development, Physiology, and Disease. CSH Perspect. Biol., 8.","DOI":"10.1101\/cshperspect.a021881"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1677\/JOE-08-0549","article-title":"The Biology of Activin: Recent Advances in Structure, Regulation and Function","volume":"202","author":"Xia","year":"2009","journal-title":"J. Endocrinol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.bbrc.2018.08.171","article-title":"Activin A Induces Leiomyoma Cell Proliferation, Extracellular Matrix (ECM) Accumulation and Myofibroblastic Transformation of Myometrial Cells via P38 MAPK","volume":"504","author":"Bao","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Yuan, C., Ni, L., and Wu, X. (2021). Activin A Activation Drives Renal Fibrosis through the STAT3 Signaling Pathway. Int. J. Biochem. Cell Biol., 134.","DOI":"10.1016\/j.biocel.2021.105950"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Li, S., Li, Z., Yin, R., Nie, J., Fu, Y., and Ying, R. (2021). Knockdown of Dual Oxidase 1 Suppresses Activin A-Induced Fibrosis in Cardiomyocytes via the Reactive Oxygen Species-Dependent Pyroptotic Pathway. Int. J. Biochem. Cell Biol., 131.","DOI":"10.1016\/j.biocel.2020.105902"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Ren, L.-L., Li, X.-J., Duan, T.-T., Li, Z.-H., Yang, J.-Z., Zhang, Y.-M., Zou, L., Miao, H., and Zhao, Y.-Y. (2023). Transforming Growth Factor-\u03b2 Signaling: From Tissue Fibrosis to Therapeutic Opportunities. Chem. Biol. Interact., 369.","DOI":"10.1016\/j.cbi.2022.110289"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1164\/rccm.200412-1620OC","article-title":"Attenuation of Bleomycin-Induced Pulmonary Fibrosis by Follistatin","volume":"172","author":"Aoki","year":"2005","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1093\/gerona\/glad033","article-title":"Challenges and Future Prospects of Targeting Myostatin\/Activin A Signaling to Treat Diseases of Muscle Loss and Metabolic Dysfunction","volume":"78","author":"Lee","year":"2023","journal-title":"J. Gerontol. Ser. A"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1016\/j.ajpath.2013.12.029","article-title":"Inhibition of Activin A Ameliorates Skeletal Muscle Injury and Rescues Contractile Properties by Inducing Efficient Remodeling in Female Mice","volume":"184","author":"Yaden","year":"2014","journal-title":"Am. J. Pathol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1164\/rccm.201802-0286OC","article-title":"Activin Type II Receptor Blockade for Treatment of Muscle Depletion in Chronic Obstructive Pulmonary Disease. A Randomized Trial","volume":"199","author":"Polkey","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1172\/JCI133678","article-title":"Biological Basis for Efficacy of Activin Receptor Ligand Traps in Myelodysplastic Syndromes","volume":"130","author":"Verma","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Li, F., Long, Y., Yu, X., Tong, Y., and Gong, L. (2022). Different Immunoregulation Roles of Activin A Compared With TGF-\u03b2. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.921366"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Rossino, G., Marchese, E., Galli, G., Verde, F., Finizio, M., Serra, M., Linciano, P., and Collina, S. (2023). Peptides as Therapeutic Agents: Challenges and Opportunities in the Green Transition Era. Molecules, 28.","DOI":"10.3390\/molecules28207165"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Cabri, W., Cantelmi, P., Corbisiero, D., Fantoni, T., Ferrazzano, L., Martelli, G., Mattellone, A., and Tolomelli, A. (2021). Therapeutic Peptides Targeting PPI in Clinical Development: Overview, Mechanism of Action and Perspectives. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.697586"},{"key":"ref_46","first-page":"100081","article-title":"Potential Role of Biopeptides in the Treatment of Idiopathic Pulmonary Fibrosis","volume":"6","author":"Karande","year":"2023","journal-title":"Health Sci. Rev."},{"key":"ref_47","first-page":"325","article-title":"Functional Analysis of the Cysteine Residues of Activin A","volume":"8","author":"Mason","year":"1994","journal-title":"Mol. Endocrinol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.tem.2005.01.003","article-title":"Antagonists of Activin Signaling: Mechanisms and Potential Biological Applications","volume":"16","author":"Harrison","year":"2005","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1093\/emboj\/cdg156","article-title":"Structures of an ActRIIB:Activin A Complex Reveal a Novel Binding Mode for TGF-\u03b2 Ligand:Receptor Interactions","volume":"22","author":"Thompson","year":"2003","journal-title":"EMBO J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1677\/joe.0.1760061","article-title":"Residues in the C-Terminal Region of Activin A Determine Specificity for Follistatin and Type II Receptor Binding","volume":"176","author":"Fischer","year":"2003","journal-title":"J. Endocrinol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s10020-021-00283-6","article-title":"TGF-\u03b2-Induced \u03b1-SMA Expression Is Mediated by C\/EBP\u03b2 Acetylation in Human Alveolar Epithelial Cells","volume":"27","author":"Ding","year":"2021","journal-title":"Mol. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"114913","DOI":"10.1016\/j.taap.2020.114913","article-title":"Honokiol: A Polyphenol Neolignan Ameliorates Pulmonary Fibrosis by Inhibiting TGF-\u03b2\/Smad Signaling, Matrix Proteins and IL-6\/CD44\/STAT3 Axis Both in vitro and in vivo","volume":"391","author":"Pulivendala","year":"2020","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Ding, Y., Hou, Y., Liu, Y., Yu, T., Cui, Y., and Nie, H. (2022). MiR-130a-3p Alleviates Inflammatory and Fibrotic Phases of Pulmonary Fibrosis Through Proinflammatory Factor TNF-\u03b1 and Profibrogenic Receptor TGF-\u0392RII. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.863646"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Ruan, H., Luan, J., Gao, S., Li, S., Jiang, Q., Liu, R., Liang, Q., Zhang, R., Zhang, F., and Li, X. (2021). Fedratinib Attenuates Bleomycin-Induced Pulmonary Fibrosis via the JAK2\/STAT3 and TGF-\u03921 Signaling Pathway. Molecules, 26.","DOI":"10.3390\/molecules26154491"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/1465-9921-10-100","article-title":"TGF-\u03921 Induced Epithelial to Mesenchymal Transition (EMT) in Human Bronchial Epithelial Cells Is Enhanced by IL-1\u03b2 but Not Abrogated by Corticosteroids","volume":"10","author":"Doerner","year":"2009","journal-title":"Respir. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/1465-9921-6-56","article-title":"TGF-\u03921 Induces Human Alveolar Epithelial to Mesenchymal Cell Transition (EMT)","volume":"6","author":"Kasai","year":"2005","journal-title":"Respir. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5013","DOI":"10.1182\/blood-2011-03-342691","article-title":"The Yin and Yang of Activin A","volume":"117","author":"Sozzani","year":"2011","journal-title":"Blood"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s40139-016-0099-1","article-title":"Fibroblast\u2014Extracellular Matrix Interactions in Tissue Fibrosis","volume":"4","author":"Frangogiannis","year":"2016","journal-title":"Curr. Pathobiol. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/s12195-017-0493-8","article-title":"Matrix Mechanics Influence Fibroblast\u2013Myofibroblast Transition by Directing the Localization of Histone Deacetylase 4","volume":"10","author":"Li","year":"2017","journal-title":"Cell. Mol. Bioeng."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1164\/rccm.200706-805OC","article-title":"Partial Inhibition of Integrin Av\u03b26 Prevents Pulmonary Fibrosis without Exacerbating Inflammation","volume":"177","author":"Horan","year":"2008","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1186\/s13148-023-01588-5","article-title":"Histone Deacetylase 3 Deletion in Alveolar Type 2 Epithelial Cells Prevents Bleomycin-Induced Pulmonary Fibrosis","volume":"15","author":"Xiong","year":"2023","journal-title":"Clin. Epigenetics"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1186\/s12931-019-1223-7","article-title":"YY1 Mediates TGF-\u03921-Induced EMT and pro-Fibrogenesis in Alveolar Epithelial Cells","volume":"20","author":"Zhang","year":"2019","journal-title":"Respir. Res."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Doolin, M.T., Smith, I.M., and Stroka, K.M. (2021). Fibroblast to Myofibroblast Transition Is Enhanced by Increased Cell Density. Mol. Biol. Cell, 32.","DOI":"10.1091\/mbc.E20-08-0536"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"D\u2019Urso, M., and Kurniawan, N.A. (2020). Mechanical and Physical Regulation of Fibroblast\u2013Myofibroblast Transition: From Cellular Mechanoresponse to Tissue Pathology. Front. Bioeng. Biotechnol., 8.","DOI":"10.3389\/fbioe.2020.609653"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Gregorio, J.D., Robuffo, I., Spalletta, S., Giambuzzi, G., Iuliis, V.D., Toniato, E., Martinotti, S., Conti, P., and Flati, V. (2020). The Epithelial-to-Mesenchymal Transition as a Possible Therapeutic Target in Fibrotic Disorders. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.607483"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"bqab207","DOI":"10.1210\/endocr\/bqab207","article-title":"PGE2 and Thrombin Induce Myofibroblast Transdifferentiation via Activin A and CTGF in Endometrial Stromal Cells","volume":"162","author":"Kusama","year":"2021","journal-title":"Endocrinology"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"D\u017eepina, P., \u0106ori\u0107, M., Perica, M.K., Ani\u010di\u0107, M.N., Grizelj, R., and Vukovi\u0107, J. (2024). Expression of Activin A in Liver Tissue and the Outcome of Patients with Biliary Atresia. Front. Pediatr., 12.","DOI":"10.3389\/fped.2024.1457837"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"He, M., Yang, T., Zhou, J., Wang, R., and Li, X. (2024). A Real-World Study of Antifibrotic Drugs-Related Adverse Events Based on the United States Food and Drug Administration Adverse Event Reporting System and VigiAccess Databases. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1310286"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Vaz, E.R., Fujimura, P.T., Araujo, G.R., da Silva, C.A.T., Silva, R.L., Cunha, T.M., Lopes-Ferreira, M., Lima, C., Ferreira, M.J., and Cunha-Junior, J.P. (2015). A Short Peptide That Mimics the Binding Domain of TGF-\u03921 Presents Potent Anti-Inflammatory Activity. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0136116"},{"key":"ref_70","first-page":"487","article-title":"Phage Display: A Laboratory Manua","volume":"76","author":"Barbas","year":"2001","journal-title":"Q. Rev. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3784","DOI":"10.1093\/nar\/gkg563","article-title":"ExPASy: The Proteomics Server for in-Depth Protein Knowledge and Analysis","volume":"31","author":"Gasteiger","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4745","DOI":"10.1021\/ct500592m","article-title":"Improved PEP-FOLD Approach for Peptide and Miniprotein Structure Prediction","volume":"10","author":"Shen","year":"2014","journal-title":"J. Chem. Theory Comput."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"W288","DOI":"10.1093\/nar\/gks419","article-title":"PEP-FOLD: An Updated de Novo Structure Prediction Server for Both Linear and Disulfide Bonded Cyclic Peptides","volume":"40","author":"Shen","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"W449","DOI":"10.1093\/nar\/gkw329","article-title":"PEP-FOLD3: Faster de Novo Structure Prediction for Linear Peptides in Solution and in Complex","volume":"44","author":"Lamiable","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"W431","DOI":"10.1093\/nar\/gkv495","article-title":"GalaxyPepDock: A Protein\u2013Peptide Docking Tool Based on Interaction Similarity and Energy Optimization","volume":"43","author":"Lee","year":"2015","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/6\/2705\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:55:18Z","timestamp":1760028918000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/6\/2705"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,17]]},"references-count":75,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["ijms26062705"],"URL":"https:\/\/doi.org\/10.3390\/ijms26062705","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,17]]}}}