{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T18:09:20Z","timestamp":1792606160662,"version":"4.5.0"},"reference-count":108,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T00:00:00Z","timestamp":1642377600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000005","name":"United States Department of Defense","doi-asserted-by":"publisher","award":["VR180066"],"award-info":[{"award-number":["VR180066"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["EY025585"],"award-info":[{"award-number":["EY025585"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Every organ develops fibrosis that compromises functions in response to infections, injuries, or diseases. The cornea is a relatively simple, avascular organ that offers an exceptional model to better understand the pathophysiology of the fibrosis response. Injury and defective regeneration of the epithelial basement membrane (EBM) or the endothelial Descemet\u2019s basement membrane (DBM) triggers the development of myofibroblasts from resident corneal fibroblasts and bone marrow-derived blood borne fibrocytes due to the increased entry of TGF beta-1\/-2 into the stroma from the epithelium and tears or residual corneal endothelium and aqueous humor. The myofibroblasts, and disordered extracellular matrix these cells produce, persist until the source of injury is removed, the EBM and\/or DBM are regenerated, or replaced surgically, resulting in decreased stromal TGF beta requisite for myofibroblast survival. A similar BM injury-related pathophysiology can underly the development of fibrosis in other organs such as skin and lung. The normal liver does not contain traditional BMs but develops sinusoidal endothelial BMs in many fibrotic diseases and models. However, normal hepatic stellate cells produce collagen type IV and perlecan that can modulate TGF beta localization and cognate receptor binding in the space of Diss\u00e9. BM-related fibrosis is deserving of more investigation in all organs.<\/jats:p>","DOI":"10.3390\/cells11020309","type":"journal-article","created":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T08:20:42Z","timestamp":1642407642000},"page":"309","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Fibrosis Is a Basement Membrane-Related Disease in the Cornea: Injury and Defective Regeneration of Basement Membranes May Underlie Fibrosis in Other Organs"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8121-960X","authenticated-orcid":false,"given":"Steven E.","family":"Wilson","sequence":"first","affiliation":[{"name":"Cole Eye Institute, I-32, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,17]]},"reference":[{"key":"ref_1","first-page":"343","article-title":"Pulmonary fibrosis, part I: Epidemiology, pathogenesis, and diagnosis","volume":"11","author":"Meyer","year":"2017","journal-title":"Expert Rev. Respir. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"108594","DOI":"10.1016\/j.exer.2021.108594","article-title":"TGF beta -1, -2 and -3 in the modulation of fibrosis in the cornea and other organs","volume":"207","author":"Wilson","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/S0161-6420(97)30306-6","article-title":"Late onset corneal haze after photorefractive keratectomy for moderate and high myopia","volume":"104","author":"Lipshitz","year":"1997","journal-title":"Ophthalmology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"337","DOI":"10.3928\/1081597X-20170126-02","article-title":"Regeneration of defective epithelial basement membrane and restoration of corneal transparency","volume":"33","author":"Marino","year":"2017","journal-title":"J. Ref. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"108325","DOI":"10.1016\/j.exer.2020.108325","article-title":"TGF\u03b21 and TGF\u03b22 proteins in corneas with and without stromal fibrosis: Delayed regeneration of epithelial barrier function and the epithelial basement membrane in corneas with stromal fibrosis","volume":"202","author":"Tye","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1167\/iovs.18-26451","article-title":"Descemet\u2019s membrane modulation of posterior corneal fibrosis","volume":"60","author":"Medeiros","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"108803","DOI":"10.1016\/j.exer.2021.108803","article-title":"Descemet\u2019s membrane injury and regeneration, and posterior corneal fibrosis in rabbits","volume":"213","author":"Sampaio","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"108137","DOI":"10.1016\/j.exer.2020.108137","article-title":"Composition, structure and function of the corneal stroma","volume":"198","author":"Espana","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"108033","DOI":"10.1016\/j.exer.2020.108033","article-title":"Bowman\u2019s layer in the cornea-structure and function and regeneration","volume":"195","author":"Wilson","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/S1350-9462(02)00065-4","article-title":"Proliferative capacity of the corneal endothelium","volume":"22","author":"Joyce","year":"2003","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"108090","DOI":"10.1016\/j.exer.2020.108090","article-title":"Descemet\u2019s membrane development, structure, function and regeneration","volume":"197","author":"Wilson","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.exer.2010.04.007","article-title":"Corneal myofibroblast generation from bone marrow-derived cells","volume":"91","author":"Barbosa","year":"2010","journal-title":"Exp. Eye Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S0014-4835(03)00050-2","article-title":"Corneal nerves: Structure, contents and function","volume":"76","author":"Marfurt","year":"2003","journal-title":"Exp. Eye Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"108502","DOI":"10.1016\/j.exer.2021.108502","article-title":"The cornea IV immunology, infection, neovascularization, and surgery chapter 1: Corneal immunology","volume":"205","author":"Mousa","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1006\/exer.1996.0038","article-title":"Epithelial injury induces keratocyte apoptosis: Hypothesized role for the interleukin-1 system in the modulation of corneal tissue organization and wound healing","volume":"62","author":"Wilson","year":"1996","journal-title":"Exp. Eye Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.exer.2018.03.025","article-title":"Posterior stromal keratocyte apoptosis triggered by mechanical endothelial injury and nidogen-1 production in the cornea","volume":"172","author":"Medeiros","year":"2018","journal-title":"Exp. Eye Res."},{"key":"ref_17","first-page":"1582","article-title":"The Fas\/Fas ligand system and other modulators of apoptosis in the cornea","volume":"37","author":"Wilson","year":"1996","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1006\/exer.1997.0371","article-title":"Apoptosis in the cornea: Further characterization of Fas-Fas ligand system","volume":"65","author":"Mohan","year":"1997","journal-title":"Exp. Eye Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0014-4835(02)00251-8","article-title":"Apoptosis, necrosis, proliferation, and myofibroblast generation in the stroma following LASIK and PRK","volume":"76","author":"Mohan","year":"2003","journal-title":"Exp. Eye Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1006\/exer.1996.0266","article-title":"Herpes simplex virus type-1 infection of corneal epithelial cells induces apoptosis of the underlying keratocytes","volume":"64","author":"Wilson","year":"1997","journal-title":"Exp. Eye Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.exer.2018.02.018","article-title":"Fibrocyte migration, differentiation and apoptosis during the corneal wound healing response to injury","volume":"170","author":"Lassance","year":"2018","journal-title":"Exp. Eye Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"108272","DOI":"10.1016\/j.exer.2020.108272","article-title":"Corneal myofibroblasts and fibrosis","volume":"201","author":"Wilson","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"59","DOI":"10.3928\/1081597X-20171128-01","article-title":"Pathophysiology of corneal scarring in persistent epithelial defects after PRK and other corneal injuries","volume":"34","author":"Wilson","year":"2018","journal-title":"J. Ref. Surg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1177\/34.1.3510247","article-title":"Models for the self-assembly of basement membrane","volume":"34","author":"Yurchenco","year":"1986","journal-title":"J. Histochem. Cytochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"50","DOI":"10.3928\/1081597X-20211007-02","article-title":"Epithelial basement membrane regeneration after PRK-induced epithelial-stromal injury in rabbits: Fibrotic vs. non-fibrotic corneal healing","volume":"38","author":"Sampaio","year":"2022","journal-title":"J. Ref. Surg."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1007\/s10059-009-0069-0","article-title":"Basement membrane proteoglycans: Modulators Par Excellence of cancer growth and angiogenesis","volume":"27","author":"Iozzo","year":"2009","journal-title":"Mol. Cells"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/0012-1606(91)90081-D","article-title":"Transforming growth factor beta type 1 binds to collagen IV of basement membrane matrix: Implications for development","volume":"143","author":"Paralkar","year":"1991","journal-title":"Dev. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.jdermsci.2005.10.005","article-title":"The bioactivity of transforming growth factor-beta1 can be regulated via binding to dermal collagens in mink lung epithelial cells","volume":"41","author":"Shibuya","year":"2006","journal-title":"J. Dermatol. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1046\/j.1432-1327.1998.2550060.x","article-title":"Mapping of the binding of platelet-derived growth factor to distinct domains of the basement membrane proteins BM-40 and perlecan and distinction from the BM-40 collagen-binding epitope","volume":"255","author":"Sasaki","year":"1998","journal-title":"Eur. J. Biochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1006\/exer.2002.2066","article-title":"TGF beta induced myofibroblast differentiation of rabbit keratocytes requires synergistic TGF beta, PDGF and integrin signaling","volume":"75","author":"Jester","year":"2002","journal-title":"Exp. Eye Res."},{"key":"ref_31","first-page":"481","article-title":"Phagocytic properties of human keratocyte cultures","volume":"20","author":"Lande","year":"1981","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.exer.2017.05.003","article-title":"Epithelial basement membrane injury and regeneration modulates corneal fibrosis after pseudomonas corneal ulcers in rabbits","volume":"161","author":"Marino","year":"2017","journal-title":"Exp. Eye Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.matbio.2017.06.003","article-title":"Injury and defective regeneration of the epithelial basement membrane in corneal fibrosis: A paradigm for fibrosis in other organs?","volume":"64","author":"Wilson","year":"2017","journal-title":"Matrix Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1016\/j.exer.2005.09.021","article-title":"Stromal haze, myofibroblasts, and surface irregularity after PRK","volume":"82","author":"Netto","year":"2006","journal-title":"Exp. Eye Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4026","DOI":"10.1167\/iovs.13-12106","article-title":"Transmission electron microscopy analysis of epithelial basement membrane repair in rabbit corneas with haze","volume":"54","author":"Torricelli","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/0012-1606(77)90304-9","article-title":"Regeneration of corneal tissue","volume":"61","author":"Cintron","year":"1977","journal-title":"Dev. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.exer.2007.06.009","article-title":"Apoptosis in the initiation, modulation and termination of the corneal wound healing response","volume":"85","author":"Wilson","year":"2007","journal-title":"Exp. Eye Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1038\/sj.jid.5700613","article-title":"Formation and function of the myofibroblast during tissue repair","volume":"127","author":"Hinz","year":"2007","journal-title":"J. Investig. Dermatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1146\/annurev-physiol-012110-142225","article-title":"Epithelial\u2013mesenchymal interactions in pulmonary fibrosis","volume":"73","author":"Chapman","year":"2011","journal-title":"Annu. Rev. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1016\/j.ajpath.2011.06.001","article-title":"Role of endothelial-mesenchymal transition (EndoMT) in the pathogenesis of fibrotic disorders","volume":"179","author":"Li","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.exer.2012.03.006","article-title":"Stromal fibroblast-bone marrow-derived cell interactions: Implications for myofibroblast development in the cornea","volume":"98","author":"Singh","year":"2012","journal-title":"Exp. Eye Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"16717","DOI":"10.1038\/s41598-020-73686-w","article-title":"Quantitative proteomic comparison of myofibroblasts derived from bone marrow or locally from the cornea","volume":"10","author":"Saikia","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/s00441-018-2934-7","article-title":"Basement membranes in the cornea and other organs that commonly develop fibrosis","volume":"374","author":"Saikia","year":"2018","journal-title":"Cell Tissue Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1002\/cphy.c170016","article-title":"Pathophysiologic mechanisms and current treatments for cutaneous sequelae of burn wounds","volume":"8","author":"Hall","year":"2017","journal-title":"Compr. Physiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1056\/NEJMra0806188","article-title":"Scleroderma","volume":"360","author":"Gabrielli","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.jdermsci.2011.10.008","article-title":"Interactions between myofibroblast differentiation and epidermogenesis in constructing human living skin equivalents","volume":"65","author":"Yang","year":"2012","journal-title":"J. Dermatol. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Liarte, S., Bernab\u00e9-Garc\u00eda, \u00c1., and Nicol\u00e1s, F.J. (2020). Role of TGF-\u03b2 in skin chronic wounds: A keratinocyte perspective. Cells, 9.","DOI":"10.3390\/cells9020306"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/0923-1811(95)00438-6","article-title":"Differential localization of TGF-beta-precursor isotypes in psoriatic human skin","volume":"11","author":"Hashimoto","year":"1996","journal-title":"J. Dermatol. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/j.celrep.2019.06.087","article-title":"Monocytes acquire the ability to prime tissue-resident T cells via IL-10-mediated TGF-\u03b2 release","volume":"28","author":"Thompson","year":"2019","journal-title":"Cell Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1002\/art.1780330507","article-title":"Secretion and binding of transforming growth factor beta by scleroderma and normal dermal fibroblasts","volume":"33","author":"Needleman","year":"1990","journal-title":"Arthritis Rheum."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"153","DOI":"10.3892\/ijmm.2016.2816","article-title":"Hypoxia drives the transition of human dermal fibroblasts to a myofibroblast-like phenotype via the TGF-\u03b21\/Smad3 pathway","volume":"39","author":"Zhao","year":"2017","journal-title":"Int. J. Mol. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.jdermsci.2010.11.015","article-title":"Epithelial-mesenchymal transition in the skin","volume":"61","author":"Nakamura","year":"2011","journal-title":"J. Dermatol. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1007\/s00441-016-2464-0","article-title":"Epithelial-mesenchymal transition in tissue repair and fibrosis","volume":"365","author":"Stone","year":"2016","journal-title":"Cell Tissue Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1111\/exd.13379","article-title":"Adipocyte-myofibroblast transition as a possible pathophysiological step in androgenetic alopecia","volume":"26","author":"Kruglikov","year":"2017","journal-title":"Exp. Dermatol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"R1113","DOI":"10.1186\/ar1790","article-title":"Shared expression of phenotypic markers in systemic sclerosis indicates a convergence of pericytes and fibroblasts to a myofibroblast lineage in fibrosis","volume":"7","author":"Rajkumar","year":"2005","journal-title":"Arthritis Res. Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s11926-006-0055-x","article-title":"The role of circulating fibrocytes in fibrosis","volume":"8","author":"Quan","year":"2006","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_57","first-page":"443","article-title":"Intraluminal fibrosis in interstitial lung disorders","volume":"122","author":"Basset","year":"1986","journal-title":"Am. J. Pathol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1590\/1414-431X20143522","article-title":"Modeling pulmonary fibrosis by abnormal expression of telomerase\/apoptosis\/collagen V in experimental usual interstitial pneumonia","volume":"47","author":"Parra","year":"2014","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1136\/thx.36.11.801","article-title":"Alveolar response to injury","volume":"36","author":"Bowden","year":"1981","journal-title":"Thorax"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1242\/jcs.113.5.859","article-title":"Assembly of the exogenous extracellular matrix during basement membrane formation by alveolar epithelial cells in vitro","volume":"113","author":"Furuyama","year":"2000","journal-title":"J. Cell Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1111\/j.1440-1827.1995.tb03488.x","article-title":"Alveolar basement membrane breaks down in diffuse alveolar damage: An immunohistochemical study","volume":"45","author":"Matsubara","year":"1995","journal-title":"Pathol. Int."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1016\/S0002-9440(10)62351-6","article-title":"Induction of epithelial-mesenchymal transition in alveolar epithelial cells by transforming growth factor-beta1: Potential role in idiopathic pulmonary fibrosis","volume":"166","author":"Willis","year":"2005","journal-title":"Am. J. Pathol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/1465-9921-6-56","article-title":"TGF-beta1 induces human alveolar epithelial to mesenchymal cell transition (EMT)","volume":"6","author":"Kasai","year":"2005","journal-title":"Respir. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.lfs.2004.06.019","article-title":"TGF-beta1 induces alveolar epithelial to mesenchymal transition in vitro","volume":"76","author":"Yao","year":"2004","journal-title":"Life Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1186\/s12931-018-0841-9","article-title":"Human alveolar epithelial cells type II are capable of TGF\u03b2-dependent epithelial-mesenchymal-transition and collagen-synthesis","volume":"19","author":"Goldmann","year":"2018","journal-title":"Respir. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"13180","DOI":"10.1073\/pnas.0605669103","article-title":"Alveolar epithelial cell mesenchymal transition develops in vivo during pulmonary fibrosis and is regulated by extracellular matrix","volume":"103","author":"Kim","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"E1475","DOI":"10.1073\/pnas.1117988108","article-title":"Multiple stromal populations contribute to pulmonary fibrosis without evidence for epithelial to mesenchymal transition","volume":"108","author":"Rock","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","first-page":"517","article-title":"EMT and interstitial lung disease: A mysterious relationship","volume":"18","author":"Kage","year":"2012","journal-title":"Curr. Opin. Pulm. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"85","DOI":"10.2353\/ajpath.2010.090517","article-title":"Fate tracing reveals the pericyte and not epithelial origin of myofibroblasts in kidney fibrosis","volume":"176","author":"Humphreys","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s12931-018-0798-8","article-title":"Fibrocytes are increased in lung and peripheral blood of patients with idiopathic pulmonary fibrosis","volume":"19","author":"Heukels","year":"2018","journal-title":"Respir. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"279","DOI":"10.4103\/1817-1737.157294","article-title":"Rapid detection of circulating fibrocytes by flowcytometry in idiopathic pulmonary fibrosis","volume":"10","author":"Alhamad","year":"2015","journal-title":"Ann. Thorac. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1164\/rccm.200810-1534OC","article-title":"Circulating fibrocytes are an indicator of poor prognosis in idiopathic pulmonary fibrosis","volume":"179","author":"Moeller","year":"2009","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1016\/j.biocel.2008.02.012","article-title":"Fibrocytes are a potential source of lung fibroblasts in idiopathic pulmonary fibrosis","volume":"40","author":"Nihlberg","year":"2008","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_74","first-page":"1754","article-title":"Rat alveolar myofibroblasts acquire alpha-smooth muscle actin expression during bleomycin-induced pulmonary fibrosis","volume":"143","author":"Vyalov","year":"1993","journal-title":"Am. J. Pathol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Piera-Velazquez, S., Mendoza, F.A., and Jimenez, S.A. (2016). Endothelial to mesenchymal transition (EndoMT) in the pathogenesis of human fibrotic diseases. J. Clin. Med., 5.","DOI":"10.3390\/jcm5040045"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/mi.2008.85","article-title":"Pulmonary fibrosis: Pathogenesis, etiology and regulation","volume":"2","author":"Wilson","year":"2009","journal-title":"Mucosal. Immunol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1136\/thx.2005.056317","article-title":"In vivo IL-10 gene delivery attenuates bleomycin induced pulmonary fibrosis by inhibiting the production and activation of TGF-beta in the lung","volume":"61","author":"Nakagome","year":"2006","journal-title":"Thorax"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.21873\/invivo.11668","article-title":"Ionizing radiation promotes epithelial-to-mesenchymal transition in lung epithelial cells by TGF-\u03b2-producing M2 macrophages","volume":"33","author":"Park","year":"2019","journal-title":"In Vivo"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1146\/annurev-physiol-022516-034356","article-title":"Mechanisms of organ injury and repair by macrophages","volume":"79","author":"Vannella","year":"2017","journal-title":"Annu. Rev. Physiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1002\/jcp.1041400226","article-title":"Production of transforming growth factor beta by human peripheral blood monocytes and neutrophils","volume":"140","author":"Grotendorst","year":"1989","journal-title":"J. Cell Physiol."},{"key":"ref_81","first-page":"352","article-title":"Cellular localization of transforming growth factor-beta expression in bleomycin-induced pulmonary fibrosis","volume":"147","author":"Zhang","year":"1995","journal-title":"Am. J. Pathol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"173","DOI":"10.3389\/fphar.2013.00173","article-title":"The epithelium in idiopathic pulmonary fibrosis: Breaking the barrier","volume":"4","author":"Camelo","year":"2014","journal-title":"Front. Pharmacol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1183\/09031936.01.00074101","article-title":"Type II alveolar epithelial cells and interstitial fibroblasts express connective tissue growth factor in IPF","volume":"17","author":"Pan","year":"2001","journal-title":"Eur. Respir. J."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Saito, A., Horie, M., and Nagase, T. (2018). TGF-b signaling in lung health and disease. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082460"},{"key":"ref_85","first-page":"905","article-title":"Alveolar wall basement membranes in bleomycin-induced pulmonary fibrosis","volume":"132","author":"Vaccaro","year":"1985","journal-title":"Am. Rev. Respir. Dis."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1247\/csf.22.603","article-title":"Assembly of basement membrane in vitro by cooperation between alveolar epithelial cells and pulmonary fibroblasts","volume":"22","author":"Furuyama","year":"1997","journal-title":"Cell Struct. Funct."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"L1004","DOI":"10.1152\/ajplung.00379.2001","article-title":"Laminin alpha-chain expression and basement membrane formation by MLE-15 respiratory epithelial cells","volume":"282","author":"Nguyen","year":"2002","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1002\/hep.510240310","article-title":"Heparan sulfate proteoglycan expression in chronic cholestatic human liver diseases","volume":"24","author":"Roskams","year":"1996","journal-title":"Hepatology"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.biomaterials.2018.07.008","article-title":"Laminin-521 promotes quiescence in isolated stellate cells from rat liver","volume":"180","author":"Zhang","year":"2018","journal-title":"Biomaterials"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.yexcr.2017.02.038","article-title":"Modulation of hepatic stellate cells and reversibility of hepatic fibrosis","volume":"352","author":"Huang","year":"2017","journal-title":"Exp. Cell Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1369\/jhc.5A6810.2006","article-title":"Hematopoietic cells are a source of nidogen-1 and nidogen-2 during mouse liver development","volume":"54","author":"Tomte","year":"2006","journal-title":"J. Histochem. Cytochem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1002\/hep.30969","article-title":"Is the Total Amount as Important as Localization and Type of Collagen in Liver Fibrosis Attributable to Steatohepatitis?","volume":"71","author":"Karsdal","year":"2020","journal-title":"Hepatology"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1002\/ar.23567","article-title":"Basement membrane type IV collagen and laminin: An overview of their biology and value as fibrosis biomarkers of liver disease","volume":"300","author":"Mak","year":"2017","journal-title":"Anat. Rec."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1002\/hep.1840140519","article-title":"The role of capillarization in hepatic failure: Studies in carbon tetrachloride-induced cirrhosis","volume":"14","author":"Martinez","year":"1991","journal-title":"Hepatology"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/S0168-8278(01)00134-9","article-title":"Modulation of collagen XVIII\/endostatin expression in lobular and biliary rat liver fibrogenesis","volume":"35","author":"Jia","year":"2001","journal-title":"J. Hepatol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1002\/ar.22694","article-title":"Codistribution of collagen type IV and laminin in liver fibrosis of elderly cadavers: Immunohistochemical marker of perisinusoidal basement membrane formation","volume":"296","author":"Mak","year":"2013","journal-title":"Anat. Rec."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1002\/path.1328","article-title":"Age-related pseudocapillarization of the human liver","volume":"200","author":"McLean","year":"2003","journal-title":"J. Pathol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1002\/ar.20661","article-title":"Old age and the hepatic sinusoid","volume":"291","author":"Warren","year":"2008","journal-title":"Anat. Rec."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1002\/path.2277","article-title":"Cellular and molecular mechanisms of fibrosis","volume":"214","author":"Wynn","year":"2008","journal-title":"J. Pathol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1165\/ajrcmb.15.2.8703482","article-title":"Plasmin regulates the activation of cell-associated latent TGF\u03b21 secreted by rat alveolar macrophages after in vivo bleomycin injury","volume":"15","author":"Khalil","year":"1996","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_101","first-page":"386","article-title":"Immunomodulatory effects of transforming growth factor-\u03b2 in the liver","volume":"3","author":"Schon","year":"2014","journal-title":"Hepatobiliary Surg. Nutr."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1182\/bloodadvances.2017010868","article-title":"Platelet TGF-\u03b21 deficiency decreases liver fibrosis in a mouse model of liver injury","volume":"2","author":"Ghafoory","year":"2018","journal-title":"Blood Adv."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1002\/cphy.c120035","article-title":"Hepatic stellate cells and liver fibrosis","volume":"3","author":"Puche","year":"2013","journal-title":"Compr. Physiol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2823","DOI":"10.1038\/ncomms3823","article-title":"Fate tracing reveals hepatic stellate cells as dominant contributors to liver fibrosis independent of its aetiology","volume":"4","author":"Mederacke","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1634\/stemcells.21-5-514","article-title":"Multiple organ engraftment by bone-marrow-derived myofibroblasts and fibroblasts in bone-marrow-transplanted mice","volume":"21","author":"Direkze","year":"2003","journal-title":"Stem Cells"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1053\/j.gastro.2004.02.025","article-title":"A significant proportion of myofibroblasts are of bone marrow origin in human liver fibrosis","volume":"126","author":"Forbes","year":"2004","journal-title":"Gastroenterology"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Taura, K., Iwaisako, K., Hatano, E., and Uemoto, S. (2016). Controversies over the epithelial-to-mesenchymal transition in liver fibrosis. J. Clin. Med., 5.","DOI":"10.3390\/jcm5010009"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Lafoz, E., Ruart, M., Anton, A., Oncins, A., and Hern\u00e1ndez-Gea, V. (2020). The endothelium as a driver of liver fibrosis and regeneration. Cells, 9.","DOI":"10.3390\/cells9040929"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/2\/309\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:02:42Z","timestamp":1760133762000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/2\/309"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,17]]},"references-count":108,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["cells11020309"],"URL":"https:\/\/doi.org\/10.3390\/cells11020309","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,17]]}}}