@article{998c5582c9624412881735a9f8240462,
title = "Two-Way Conversion between Lipogenic and Myogenic Fibroblastic Phenotypes Marks the Progression and Resolution of Lung Fibrosis",
abstract = "Idiopathic pulmonary fibrosis (IPF) is a form of progressive interstitial lung disease with unknown etiology. Due to a lack of effective treatment, IPF is associated with a high mortality rate. The hallmark feature of this disease is the accumulation of activated myofibroblasts that excessively deposit extracellular matrix proteins, thus compromising lung architecture and function and hindering gas exchange. Here we investigated the origin of activated myofibroblasts and the molecular mechanisms governing fibrosis formation and resolution. Genetic engineering in mice enables the time-controlled labeling and monitoring of lipogenic or myogenic populations of lung fibroblasts during fibrosis formation and resolution. Our data demonstrate a lipogenic-to-myogenic switch in fibroblastic phenotype during fibrosis formation. Conversely, we observed a myogenic-to-lipogenic switch during fibrosis resolution. Analysis of human lung tissues and primary human lung fibroblasts indicates that this fate switching is involved in IPF pathogenesis, opening potential therapeutic avenues to treat patients.",
author = "{El Agha}, Elie and Alena Moiseenko and Vahid Kheirollahi and {De Langhe}, Stijn and Slaven Crnkovic and Grazyna Kwapiszewska and Djuro Kosanovic and Felix Schwind and Schermuly, {Ralph T.} and Ingrid Henneke and MacKenzie, {Bre Anne} and Jennifer Quantius and Susanne Herold and Aglaia Ntokou and Katrin Ahlbrecht and Morty, {Rory E.} and Andreas G{\"u}nther and Werner Seeger and Saverio Bellusci",
note = "Funding Information: We would like to thank Dr. Robert Voswinckel, Dr. Friederike Klein, and Dr. Isabelle Salwig for their contribution in generating and validating the Adrp Cre-ERT2 mice. We also thank Dr. Athanasios Fysikopoulos for his help with confocal microscopy. We also acknowledge Dr. Jochen Wilhelm for his help with the gene arrays and Stefanie Hezel, Ewa Bieniek, Stephanie Viehmann, Kerstin Goth, and Jana Rostkovius for their technical support. E.E.A. acknowledges the support of the Excellence Cluster Cardio-Pulmonary System (ECCPS) and the Universit{\"a}tsklinikum Giessen und Marburg (UKGM) . S.B. was supported by grants from the Deutsche Forschungsgemeinschaft ( DFG , BE4443/4-1 , BE4443/6-1 , and CRC1213 ), Landes-Offensive zur Entwicklung Wissenschaftlich-{\"o}konomischer Exzellenz (LOEWE) , UKGM , the Universities of Giessen and Marburg Lung Center (UGMLC) , the German Center for Lung Research ( DZL ), COST ( BM1201 ) and the NIH/NHLBI ( 1R01HL086322-01A2 and HL107307 ). J.Q. and S.H. acknowledge the support of the DZL, ECCPS, UGMLC, DFG ( SFB1021 C05 and SFB TR84 B2 ). S.B. and S.H. acknowledge the support of the UKGM (FOKOOPV). S.D.L. acknowledges the support of NIH/NHLBI ( R01HL126732 , R01HL132156 ), March of Dimes ( 1-FY15-352 ), and the pulmonary fibrosis foundation (The Albert Rose established investigator award). Funding Information: We would like to thank Prof. Thomas Braun, Dr. Martin Szibor, Dr. Robert Voswinckel, and Dr. Friederike Klein for their contribution in generating and validating the AdrpCre-ERT2 mice. We also thank Dr. Athanasios Fysikopoulos for his help with confocal microscopy. We also acknowledge Dr. Jochen Wilhelm for his help with the gene arrays and Stefanie Hezel, Ewa Bieniek, Stephanie Viehmann, Kerstin Goth, and Jana Rostkovius for their technical support. E.E.A. acknowledges the support of the Excellence Cluster Cardio-Pulmonary System (ECCPS) and the Universit?tsklinikum Giessen und Marburg (UKGM). S.B. was supported by grants from the Deutsche Forschungsgemeinschaft (DFG, BE4443/4-1, BE4443/6-1, and CRC1213), Landes-Offensive zur Entwicklung Wissenschaftlich-?konomischer Exzellenz (LOEWE), UKGM, the Universities of Giessen and Marburg Lung Center (UGMLC), the German Center for Lung Research (DZL), COST (BM1201) and the NIH/NHLBI (1R01HL086322-01A2 and HL107307). J.Q. and S.H. acknowledge the support of the DZL, ECCPS, UGMLC, DFG (SFB1021 C05 and SFB TR84 B2). S.B. and S.H. acknowledge the support of the UKGM (FOKOOPV). S.D.L. acknowledges the support of NIH/NHLBI (R01HL126732, R01HL132156), March of Dimes (1-FY15-352), and the pulmonary fibrosis foundation (The Albert Rose established investigator award). Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = feb,
day = "2",
doi = "10.1016/j.stem.2016.10.004",
language = "English (US)",
volume = "20",
pages = "261--273.e3",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "2",
}