{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:35:06Z","timestamp":1788950106218,"version":"build-2803163510"},"reference-count":50,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":365,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL127001"],"award-info":[{"award-number":["R01HL127001"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R03HL095402"],"award-info":[{"award-number":["R03HL095402"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100003284","name":"Pulmonary Fibrosis Foundation","doi-asserted-by":"publisher","award":["F32HL154525-01"],"award-info":[{"award-number":["F32HL154525-01"]}],"id":[{"id":"10.13039\/100003284","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001003","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001003","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ajp.amjpathol.org","clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The American Journal of Pathology"],"published-print":{"date-parts":[[2025,4]]},"DOI":"10.1016\/j.ajpath.2024.12.015","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T11:19:33Z","timestamp":1737544773000},"page":"626-638","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":19,"title":["Piezo2 Is a Key Mechanoreceptor in Lung Fibrosis that Drives Myofibroblast Differentiation"],"prefix":"10.1016","volume":"195","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7301-7880","authenticated-orcid":false,"given":"Margaret A.T.","family":"Freeberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4250-6133","authenticated-orcid":false,"given":"Sarah V.","family":"Camus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4542-7238","authenticated-orcid":false,"given":"Valentina","family":"Robila","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apostolos","family":"Perelas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7177-3041","authenticated-orcid":false,"given":"Thomas H.","family":"Thatcher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5101-634X","authenticated-orcid":false,"given":"Patricia J.","family":"Sime","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ajpath.2024.12.015_bib1","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1586\/17476348.2013.838015","article-title":"New treatment and markers of prognosis for idiopathic pulmonary fibrosis: lessons learned from translational research","volume":"7","author":"Baroke","year":"2013","journal-title":"Expert Rev Respir Med"},{"key":"10.1016\/j.ajpath.2024.12.015_bib2","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1378\/chest.10-2572","article-title":"Long-term course and prognosis of idiopathic pulmonary fibrosis in the new millennium","volume":"140","author":"Nathan","year":"2011","journal-title":"Chest"},{"key":"10.1016\/j.ajpath.2024.12.015_bib3","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1164\/ajrccm.149.2.8306044","article-title":"Determinants of survival in idiopathic pulmonary fibrosis","volume":"149","author":"Schwartz","year":"1994","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.ajpath.2024.12.015_bib4","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.mam.2018.08.004","article-title":"Developmental pathways in the pathogenesis of lung fibrosis","volume":"65","author":"Chanda","year":"2019","journal-title":"Mol Aspects Med"},{"key":"10.1016\/j.ajpath.2024.12.015_bib5","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.ceb.2008.06.008","article-title":"Collagen fibrillogenesis: fibronectin, integrins, and minor collagens as organizers and nucleators","volume":"20","author":"Kadler","year":"2008","journal-title":"Curr Opin Cell Biol"},{"key":"10.1016\/j.ajpath.2024.12.015_bib6","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1016\/S1286-4579(99)00250-6","article-title":"TGF-beta and fibrosis","volume":"1","author":"Branton","year":"1999","journal-title":"Microbes Infect"},{"key":"10.1016\/j.ajpath.2024.12.015_bib7","doi-asserted-by":"crossref","first-page":"6083","DOI":"10.1074\/jbc.M115.712380","article-title":"Matrix-driven myosin II mediates the pro-fibrotic fibroblast phenotype","volume":"291","author":"Southern","year":"2016","journal-title":"J Biol Chem"},{"key":"10.1016\/j.ajpath.2024.12.015_bib8","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1016\/j.ajpath.2012.02.004","article-title":"Recent developments in myofibroblast biology: paradigms for connective tissue remodeling","volume":"180","author":"Hinz","year":"2012","journal-title":"Am J Pathol"},{"key":"10.1016\/j.ajpath.2024.12.015_bib9","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1083\/jcb.201004082","article-title":"Feedback amplification of fibrosis through matrix stiffening and COX-2 suppression","volume":"190","author":"Liu","year":"2010","journal-title":"J Cell Biol"},{"key":"10.1016\/j.ajpath.2024.12.015_bib10","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1164\/rccm.201204-0754OC","article-title":"Acellular normal and fibrotic human lung matrices as a culture system for in\u00a0vitro investigation","volume":"186","author":"Booth","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.ajpath.2024.12.015_bib11","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ajpath.2020.09.008","article-title":"Mechanical feed-forward loops contribute to idiopathic pulmonary fibrosis","volume":"191","author":"Freeberg","year":"2021","journal-title":"Am J Pathol"},{"key":"10.1016\/j.ajpath.2024.12.015_bib12","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/35074532","article-title":"Force and focal adhesion assembly: a close relationship studied using elastic micropatterned substrates","volume":"3","author":"Balaban","year":"2001","journal-title":"Nat Cell Biol"},{"key":"10.1016\/j.ajpath.2024.12.015_bib13","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1083\/jcb.201609037","article-title":"Integrin-mediated mechanotransduction","volume":"215","author":"Sun","year":"2016","journal-title":"J Cell Biol"},{"key":"10.1016\/j.ajpath.2024.12.015_bib14","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1039\/c2ib00149g","article-title":"The mechanical memory of lung myofibroblasts","volume":"4","author":"Balestrini","year":"2012","journal-title":"Integr Biol (Camb)"},{"key":"10.1016\/j.ajpath.2024.12.015_bib15","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1007\/s11926-009-0017-1","article-title":"Tissue stiffness, latent TGF-beta1 activation, and mechanical signal transduction: implications for the pathogenesis and treatment of fibrosis","volume":"11","author":"Hinz","year":"2009","journal-title":"Curr Rheumatol Rep"},{"key":"10.1016\/j.ajpath.2024.12.015_bib16","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1016\/j.cub.2011.11.037","article-title":"The single-molecule mechanics of the latent TGF-beta1 complex","volume":"21","author":"Buscemi","year":"2011","journal-title":"Curr Biol"},{"key":"10.1016\/j.ajpath.2024.12.015_bib17","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1126\/science.1193270","article-title":"Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels","volume":"330","author":"Coste","year":"2010","journal-title":"Science"},{"key":"10.1016\/j.ajpath.2024.12.015_bib18","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1146\/annurev-biochem-081720-023244","article-title":"The form and function of PIEZO2","volume":"90","author":"Szczot","year":"2021","journal-title":"Annu Rev Biochem"},{"key":"10.1016\/j.ajpath.2024.12.015_bib19","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1038\/s41598-018-38376-8","article-title":"Functional expression of the mechanosensitive PIEZO1 channel in primary endometrial epithelial cells and endometrial organoids","volume":"9","author":"Hennes","year":"2019","journal-title":"Sci Rep"},{"key":"10.1016\/j.ajpath.2024.12.015_bib20","doi-asserted-by":"crossref","first-page":"2760","DOI":"10.1016\/j.celrep.2017.11.035","article-title":"Cell-type-specific splicing of Piezo2 regulates mechanotransduction","volume":"21","author":"Szczot","year":"2017","journal-title":"Cell Rep"},{"key":"10.1016\/j.ajpath.2024.12.015_bib21","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.jare.2022.12.006","article-title":"Mechanosensitive ion channel Piezo1 mediates mechanical ventilation-exacerbated ARDS-associated pulmonary fibrosis","volume":"53","author":"Fang","year":"2023","journal-title":"J Adv Res"},{"key":"10.1016\/j.ajpath.2024.12.015_bib22","first-page":"115","article-title":"Isolation and phenotypic characterization of lung fibroblasts","volume":"117","author":"Baglole","year":"2005","journal-title":"Methods Mol Med"},{"key":"10.1016\/j.ajpath.2024.12.015_bib23","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1080\/01902140600817465","article-title":"Oropharyngeal aspiration of a silica suspension produces a superior model of silicosis in the mouse when compared to intratracheal instillation","volume":"32","author":"Lakatos","year":"2006","journal-title":"Exp Lung Res"},{"key":"10.1016\/j.ajpath.2024.12.015_bib24","doi-asserted-by":"crossref","first-page":"16586","DOI":"10.1073\/pnas.0606894103","article-title":"A common mechanism underlies stretch activation and receptor activation of TRPC6 channels","volume":"103","author":"Spassova","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.ajpath.2024.12.015_bib25","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1080\/19336950.2017.1279370","article-title":"Mechanosensitive ion channel Piezo2 is inhibited by D-GsMTx4","volume":"11","author":"Alcaino","year":"2017","journal-title":"Channels (Austin)"},{"key":"10.1016\/j.ajpath.2024.12.015_bib26","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.aba1983","article-title":"Single-cell RNA-seq reveals ectopic and aberrant lung-resident cell populations in idiopathic pulmonary fibrosis","volume":"6","author":"Adams","year":"2020","journal-title":"Sci Adv"},{"key":"10.1016\/j.ajpath.2024.12.015_bib27","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-022-16344-7","article-title":"Time and phenotype-dependent transcriptome analysis in AAV-TGFbeta1 and bleomycin-induced lung fibrosis models","volume":"12","author":"Strobel","year":"2022","journal-title":"Sci Rep"},{"key":"10.1016\/j.ajpath.2024.12.015_bib28","article-title":"Loss of Fas signaling in fibroblasts impairs homeostatic fibrosis resolution and promotes persistent pulmonary fibrosis","volume":"6","author":"Redente","year":"2020","journal-title":"JCI Insight"},{"key":"10.1016\/j.ajpath.2024.12.015_bib29","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1038\/s41467-020-15647-5","article-title":"Collagen-producing lung cell atlas identifies multiple subsets with distinct localization and relevance to fibrosis","volume":"11","author":"Tsukui","year":"2020","journal-title":"Nat Commun"},{"key":"10.1016\/j.ajpath.2024.12.015_bib30","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1038\/s41586-024-07660-1","article-title":"Alveolar fibroblast lineage orchestrates lung inflammation and fibrosis","volume":"631","author":"Tsukui","year":"2024","journal-title":"Nature"},{"key":"10.1016\/j.ajpath.2024.12.015_bib31","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1113\/jphysiol.1985.sp015699","article-title":"Mechanotransducer ion channels in chick skeletal muscle: the effects of extracellular pH","volume":"363","author":"Guharay","year":"1985","journal-title":"J Physiol"},{"key":"10.1016\/j.ajpath.2024.12.015_bib32","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1161\/CIRCRESAHA.120.316958","article-title":"Myofibroblasts and fibrosis: mitochondrial and metabolic control of cellular differentiation","volume":"127","author":"Gibb","year":"2020","journal-title":"Circ Res"},{"key":"10.1016\/j.ajpath.2024.12.015_bib33","doi-asserted-by":"crossref","first-page":"4509","DOI":"10.1038\/s41467-019-12103-x","article-title":"Mitochondrial calcium exchange links metabolism with the epigenome to control cellular differentiation","volume":"10","author":"Lombardi","year":"2019","journal-title":"Nat Commun"},{"key":"10.1016\/j.ajpath.2024.12.015_bib34","doi-asserted-by":"crossref","first-page":"2390","DOI":"10.1016\/j.yexcr.2010.04.033","article-title":"Regulation of myofibroblast activities: calcium pulls some strings behind the scene","volume":"316","author":"Follonier Castella","year":"2010","journal-title":"Exp Cell Res"},{"key":"10.1016\/j.ajpath.2024.12.015_bib35","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1165\/rcmb.2014-0269TR","article-title":"Calcium homeostasis and ionic mechanisms in pulmonary fibroblasts","volume":"53","author":"Janssen","year":"2015","journal-title":"Am J Respir Cell Mol Biol"},{"key":"10.1016\/j.ajpath.2024.12.015_bib36","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1016\/j.neuron.2015.08.032","article-title":"Mechanically activated ion channels","volume":"87","author":"Ranade","year":"2015","journal-title":"Neuron"},{"key":"10.1016\/j.ajpath.2024.12.015_bib37","doi-asserted-by":"crossref","first-page":"5225","DOI":"10.1172\/JCI75331","article-title":"TRPV4 mediates myofibroblast differentiation and pulmonary fibrosis in mice","volume":"124","author":"Rahaman","year":"2014","journal-title":"J Clin Invest"},{"key":"10.1016\/j.ajpath.2024.12.015_bib38","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1165\/rcmb.2022-0446ED","article-title":"TRP channels in pulmonary fibrosis: variety is a spice of life","volume":"68","author":"Scheraga","year":"2023","journal-title":"Am J Respir Cell Mol Biol"},{"key":"10.1016\/j.ajpath.2024.12.015_bib39","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioadv.2023.213516","article-title":"Mechanical activation of lung epithelial cells through the ion channel Piezo1 activates the metalloproteinases ADAM10 and ADAM17 and promotes growth factor and adhesion molecule release","volume":"152","author":"Grannemann","year":"2023","journal-title":"Biomater Adv"},{"key":"10.1016\/j.ajpath.2024.12.015_bib40","doi-asserted-by":"crossref","first-page":"L547","DOI":"10.1152\/ajplung.00356.2023","article-title":"Piezo channels modulate human lung fibroblast function","volume":"327","author":"Zheng","year":"2024","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"10.1016\/j.ajpath.2024.12.015_bib41","doi-asserted-by":"crossref","first-page":"L542","DOI":"10.1152\/ajplung.00008.2023","article-title":"Piezo channels in stretch effects on developing human airway smooth muscle","volume":"325","author":"Kelley","year":"2023","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"10.1016\/j.ajpath.2024.12.015_bib42","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2221958120","article-title":"Membrane stretch as the mechanism of activation of PIEZO1 ion channels in chondrocytes","volume":"120","author":"Savadipour","year":"2023","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.ajpath.2024.12.015_bib43","doi-asserted-by":"crossref","first-page":"C728","DOI":"10.1152\/ajpcell.00544.2022","article-title":"The role of PIEZO ion channels in the musculoskeletal system","volume":"324","author":"Savadipour","year":"2023","journal-title":"Am J Physiol Cell Physiol"},{"key":"10.1016\/j.ajpath.2024.12.015_bib44","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2001611118","article-title":"Inflammatory signaling sensitizes Piezo1 mechanotransduction in articular chondrocytes as a pathogenic feed-forward mechanism in osteoarthritis","volume":"118","author":"Lee","year":"2021","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.ajpath.2024.12.015_bib45","doi-asserted-by":"crossref","first-page":"E5114","DOI":"10.1073\/pnas.1414298111","article-title":"Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity to articular cartilage","volume":"111","author":"Lee","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.ajpath.2024.12.015_bib46","article-title":"Loss of stretch-activated channels, PIEZOs, accelerates non-small cell lung cancer progression and cell migration","volume":"39","author":"Huang","year":"2019","journal-title":"Biosci Rep"},{"key":"10.1016\/j.ajpath.2024.12.015_bib47","doi-asserted-by":"crossref","first-page":"9909","DOI":"10.3390\/ijms23179909","article-title":"Mechano-sensing channel PIEZO2 enhances invasive phenotype in triple-negative breast cancer","volume":"23","author":"Katsuta","year":"2022","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.ajpath.2024.12.015_bib48","doi-asserted-by":"crossref","first-page":"4704","DOI":"10.1111\/j.1742-4658.2011.08346.x","article-title":"Extracellular TG2: emerging functions and regulation","volume":"278","author":"Belkin","year":"2011","journal-title":"FEBS J"},{"key":"10.1016\/j.ajpath.2024.12.015_bib49","doi-asserted-by":"crossref","DOI":"10.14814\/phy2.16012","article-title":"Transglutaminase 2 knockout mice are protected from bleomycin-induced lung fibrosis with preserved lung function and reduced metabolic derangements","volume":"12","author":"Freeberg","year":"2024","journal-title":"Physiol Rep"},{"key":"10.1016\/j.ajpath.2024.12.015_bib50","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1164\/rccm.201101-0013OC","article-title":"Transglutaminase 2 and its role in pulmonary fibrosis","volume":"184","author":"Olsen","year":"2011","journal-title":"Am J Respir Crit Care Med"}],"container-title":["The American Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002944025000288?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002944025000288?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:48:10Z","timestamp":1775004490000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0002944025000288"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":50,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["S0002944025000288"],"URL":"https:\/\/doi.org\/10.1016\/j.ajpath.2024.12.015","relation":{},"ISSN":["0002-9440"],"issn-type":[{"value":"0002-9440","type":"print"}],"subject":[],"published":{"date-parts":[[2025,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Piezo2 Is a Key Mechanoreceptor in Lung Fibrosis that Drives Myofibroblast Differentiation","name":"articletitle","label":"Article Title"},{"value":"The American Journal of Pathology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ajpath.2024.12.015","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 American Society for Investigative Pathology. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}