{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T16:15:48Z","timestamp":1778170548929,"version":"3.51.4"},"reference-count":64,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T00:00:00Z","timestamp":1660608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"T32 HL066988"},{"name":"NIH LRP"},{"name":"The Pulmonary Fibrosis Foundation"},{"name":"The Guy Solimano and Greg Chandler Fund"},{"name":"The Parker B. Francis Fellowship Award"},{"name":"IIA from Boehringer-Ingelheim"},{"name":"DOM Faculty Pilot Project Award"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Idiopathic pulmonary fibrosis (IPF) is a disease characterized by irreversible lung scarring. The pathophysiology is not fully understood, but the working hypothesis postulates that a combination of epithelial injury and myofibroblast differentiation drives progressive pulmonary fibrosis. We previously demonstrated that a reduction in extracellular pH activates latent TGF-\u03b21, and that TGF-\u03b21 then drives its own activation, creating a feed-forward mechanism that propagates myofibroblast differentiation. Given the important roles of extracellular pH in the progression of pulmonary fibrosis, we sought to identify whether pH mediates other cellular phenotypes independent of TGF-\u03b21. Proton-sensing G-protein coupled receptors are activated by acidic environments, but their role in fibrosis has not been studied. Here, we report that the Ovarian Cancer G-Protein Coupled Receptor1 (OGR1 or GPR68) has dual roles in both promoting and mitigating pulmonary fibrosis. We demonstrate that OGR1 protein expression is significantly reduced in lung tissue from patients with IPF and that TGF-\u03b21 decreases OGR1 expression. In fibroblasts, OGR1 inhibits myofibroblast differentiation and does not contribute to inflammation. However, in epithelial cells, OGR1 promotes epithelial to mesenchymal transition (EMT) and inflammation. We then demonstrate that sub-cellular localization and alternative signaling pathways may be responsible for the differential effect of OGR1 in each cell type. Our results suggest that strategies to selectively target OGR1 expression may represent a novel therapeutic strategy for pulmonary fibrosis.<\/jats:p>","DOI":"10.3390\/cells11162540","type":"journal-article","created":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T23:44:25Z","timestamp":1660693465000},"page":"2540","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Cell-Type-Specific Effects of the Ovarian Cancer G-Protein Coupled Receptor (OGR1) on Inflammation and Fibrosis; Potential Implications for Idiopathic Pulmonary Fibrosis"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0626-8118","authenticated-orcid":false,"given":"David J.","family":"Nagel","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley R.","family":"Rackow","sequence":"additional","affiliation":[{"name":"Laboratory Medicine, Department of Pathology, Division of Clinical Chemistry, Johns Hopkins University, Baltimore, MD 21287, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Yao","family":"Ku","sequence":"additional","affiliation":[{"name":"BMW of North America, Woodcliff Lake, NJ 07675, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tyler J.","family":"Bell","sequence":"additional","affiliation":[{"name":"Department of Environmental Medicine, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia J.","family":"Sime","sequence":"additional","affiliation":[{"name":"Department of Medicine, Virginia Commonwealth University Health System, Richmond, VA 23298, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert Matthew","family":"Kottmann","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1164\/rccm.201006-0894CI","article-title":"Clinical Course and Prediction of Survival in Idiopathic Pulmonary Fibrosis","volume":"183","author":"Ley","year":"2011","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1186\/s12931-021-01791-z","article-title":"Global incidence and prevalence of idiopathic pulmonary fibrosis","volume":"22","author":"Maher","year":"2021","journal-title":"Respir. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1056\/NEJMoa1402582","article-title":"A Phase 3 Trial of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis","volume":"370","author":"King","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1056\/NEJMoa1402584","article-title":"Efficacy and Safety of Nintedanib in Idiopathic Pulmonary Fibrosis","volume":"370","author":"Richeldi","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_5","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_6","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.2353\/ajpath.2007.070112","article-title":"The Myofibroblast: One Function, Multiple Origins","volume":"170","author":"Hinz","year":"2007","journal-title":"Am. J. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2730","DOI":"10.1091\/mbc.12.9.2730","article-title":"Alpha-Smooth Muscle Actin Expression Upregulates Fibroblast Contractile Activity","volume":"12","author":"Hinz","year":"2001","journal-title":"Mol. Biol. Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1097\/00005373-198310000-00001","article-title":"The Myofibroblast Anchoring Strand\u2014The Fibronectin Connection in Wound Healing and the Possible Loci of Collagen Fibril Assembly","volume":"23","author":"Baur","year":"1983","journal-title":"J. Trauma Inj. Infect. Crit. Care"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1002\/path.1427","article-title":"The myofibroblast in wound healing and fibrocontractive diseases","volume":"200","author":"Gabbiani","year":"2003","journal-title":"J. Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"H2924","DOI":"10.1152\/ajpheart.00153.2006","article-title":"Cardiac myofibroblasts differentiated in 3D culture exhibit distinct changes in collagen I production, processing, and matrix deposition","volume":"291","author":"Poobalarahi","year":"2006","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1042\/BST0350661","article-title":"TGF-\u03b2, Smad3 and the process of progressive fibrosis","volume":"35","author":"Gauldie","year":"2007","journal-title":"Biochem. Soc. Trans."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1111\/j.1440-1843.2009.01624.x","article-title":"Determinants of initiation and progression of idiopathic pulmonary fibrosis","volume":"14","author":"Kottmann","year":"2009","journal-title":"Respirology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1172\/JCI119590","article-title":"Adenovector-mediated gene transfer of active transforming growth factor-beta1 induces prolonged severe fibrosis in rat lung","volume":"100","author":"Sime","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1042\/bj3130343","article-title":"Structural characteriazation of the latent complex between transforming growth factor beta 1 and beta 1-latency-associated peptide","volume":"313","author":"McMahon","year":"1996","journal-title":"Biochem. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1242\/jcs.00229","article-title":"Making sense of latent TGF-beta activation","volume":"116","author":"Annes","year":"2003","journal-title":"J. Cell Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1002\/stem.150190","article-title":"TGF-beta latency: Biological significance and mechanisms of activation","volume":"15","author":"Gleizes","year":"1997","journal-title":"Stem Cells"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1513\/pats.201201-003AW","article-title":"TGF-beta activation and lung fibrosis","volume":"9","author":"Tatler","year":"2012","journal-title":"Proc. Am. Thorac. Soc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.ejcb.2008.01.012","article-title":"Integrins and the activation of latent transforming growth factor beta1\u2014An intimate relationship","volume":"87","author":"Wipff","year":"2008","journal-title":"Eur. J. Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1083\/jcb.200704042","article-title":"Myofibroblast contraction activates latent TGF-beta1 from the extracellular matrix","volume":"179","author":"Wipff","year":"2007","journal-title":"J. Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"L1305","DOI":"10.1152\/ajplung.00058.2015","article-title":"Pharmacologic inhibition of lactate production prevents myofibroblast differentiation","volume":"309","author":"Kottmann","year":"2015","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.canlet.2016.03.031","article-title":"G protein-coupled receptors as promising cancer targets","volume":"376","author":"Liu","year":"2016","journal-title":"Cancer Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1007\/s40265-017-0738-9","article-title":"Pharmacotherapeutic Targeting of G Protein-Coupled Receptors in Oncology: Examples of Approved Therapies and Emerging Concepts","volume":"77","author":"Lappano","year":"2017","journal-title":"Drugs"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.pupt.2012.06.005","article-title":"Regulation of GPCR-mediated smooth muscle contraction: Implications for asthma and pulmonary hypertension","volume":"26","author":"Wright","year":"2013","journal-title":"Pulm. Pharmacol. Ther."},{"key":"ref_24","first-page":"981","article-title":"The GPCR OGR1 (GPR68) mediates diverse signalling and contraction of airway smooth muscle in response to small reductions in extracellular pH","volume":"166","author":"Saxena","year":"2011","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1159\/000517474","article-title":"A Novel OGR1 (GPR68) Inhibitor Attenuates Inflammation in Murine Models of Colitis","volume":"6","author":"Busenhart","year":"2021","journal-title":"Inflamm. Intest. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1038\/s41598-020-57657-9","article-title":"Activation of pH-Sensing Receptor OGR1 (GPR68) Induces ER Stress Via the IRE1\u03b1\/JNK Pathway in an Intestinal Epithelial Cell Model","volume":"10","author":"Maeyashiki","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1016\/j.cellsig.2005.06.002","article-title":"Proton-sensing and lysolipid-sensitive G-protein-coupled receptors: A novel type of multi-functional receptors","volume":"17","author":"Tomura","year":"2005","journal-title":"Cell. Signal."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/nature01905","article-title":"Proton-sensing G-protein-coupled receptors","volume":"425","author":"Ludwig","year":"2003","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"42484","DOI":"10.1074\/jbc.M406561200","article-title":"G2A Is a Proton-sensing G-protein-coupled Receptor Antagonized by Lysophosphatidylcholine","volume":"279","author":"Murakami","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"45626","DOI":"10.1074\/jbc.M406966200","article-title":"TDAG8 Is a Proton-sensing and Psychosine-sensitive G-protein-coupled Receptor","volume":"279","author":"Wang","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1080\/10799890600932220","article-title":"Receptors for protons or lipid messengers or both?","volume":"26","author":"Seuwen","year":"2006","journal-title":"J. Recept. Signal Transduct. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1006\/geno.1996.0377","article-title":"Identification of Human OGR1, a Novel G Protein-Coupled Receptor That Maps to Chromosome 14","volume":"35","author":"Xu","year":"1996","journal-title":"Genomics"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1083\/jcb.153.2.429","article-title":"Identification of a Molecular Target of Psychosine and Its Role in Globoid Cell Formation","volume":"153","author":"Im","year":"2001","journal-title":"J. Cell Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1111\/j.1745-7254.2005.00237.x","article-title":"Two ligands for a GPCR, proton vs lysolipid","volume":"26","author":"Im","year":"2005","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1093\/jnci\/djm107","article-title":"Ovarian cancer G protein-coupled receptor 1, a new metastasis suppressor gene in prostate cancer","volume":"99","author":"Singh","year":"2007","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1750-2187-8-6","article-title":"Ovarian cancer G protein coupled receptor 1 suppresses cell migration of MCF7 breast cancer cells via a Galpha12\/13-Rho-Rac1 pathway","volume":"8","author":"Li","year":"2013","journal-title":"J. Mol. Signal."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1002\/jbmr.2030","article-title":"Ovarian Cancer G protein-Coupled Receptor 1 Is Involved in Acid-Induced Apoptosis of Endplate Chondrocytes in Intervertebral Discs","volume":"29","author":"Yuan","year":"2014","journal-title":"J. Bone Miner. Res."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Li, H., Wang, D., Singh, L.S., Berk, M., Tan, H., Zhao, Z., Steinmetz, R., Kirmani, K., Wei, G., and Xu, Y. (2009). Abnormalities in Osteoclastogenesis and Decreased Tumorigenesis in Mice Deficient for Ovarian Cancer G Protein-Coupled Receptor 1. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0005705"},{"key":"ref_39","first-page":"1269","article-title":"G Protein-coupled pH-sensing Receptor OGR1 Is a Regulator of Intestinal Inflammation","volume":"21","author":"Wang","year":"2015","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_40","first-page":"1348","article-title":"Intestinal Activation of pH-Sensing Receptor OGR1 [GPR68] Contributes to Fibrogenesis","volume":"12","author":"Hutter","year":"2018","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1096\/fj.201700555R","article-title":"Biased signaling of the proton-sensing receptor OGR1 by benzodiazepines","volume":"32","author":"Pera","year":"2018","journal-title":"FASEB J."},{"key":"ref_42","first-page":"115","article-title":"Isolation and phenotypic characterization of lung fibroblasts","volume":"117","author":"Baglole","year":"2005","journal-title":"Methods Mol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/35010529","article-title":"Sphingosylphosphorylcholine is a ligand for ovarian cancer G-protein-coupled receptor 1","volume":"2","author":"Xu","year":"2000","journal-title":"Nat. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"L887","DOI":"10.1152\/ajplung.00451.2020","article-title":"The Idiopathic Pulmonary Fibrosis Cell Atlas","volume":"319","author":"Neumark","year":"2020","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_45","first-page":"469","article-title":"A novel transforming growth factor beta response element controls the expression of the connective tissue growth factor gene","volume":"7","author":"Grotendorst","year":"1996","journal-title":"Cell Growth Differ. Mol. Biol. J. Am. Assoc. Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1091\/mbc.e04-08-0658","article-title":"TGF-beta and the Smad signaling pathway support transcriptomic reprogramming during epithelial-mesenchymal cell transition","volume":"16","author":"Valcourt","year":"2005","journal-title":"Mol. Biol. Cell"},{"key":"ref_47","first-page":"ec181","article-title":"G Protein-Coupled Receptor Signaling in the Nucleus","volume":"1","author":"Gough","year":"2008","journal-title":"Sci. Signal."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"963","DOI":"10.7326\/0003-4819-142-12_Part_1-200506210-00005","article-title":"The Clinical Course of Patients with Idiopathic Pulmonary Fibrosis","volume":"142","author":"Martinez","year":"2005","journal-title":"Ann. Intern. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1016\/j.chest.2016.07.027","article-title":"Therapeutic Approach to Adult Fibrotic Lung Diseases","volume":"150","author":"Adegunsoye","year":"2016","journal-title":"Chest"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"12384","DOI":"10.1074\/jbc.M208544200","article-title":"Myofibroblast Differentiation by Transforming Growth Factor-\u03b21 Is Dependent on Cell Adhesion and Integrin Signaling via Focal Adhesion Kinase","volume":"278","author":"Thannickal","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1056\/NEJM199411103311907","article-title":"Transforming growth factor beta in tissue fibrosis","volume":"331","author":"Border","year":"1994","journal-title":"N. Engl. J. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1164\/rccm.201201-0084OC","article-title":"Lactic acid is elevated in idiopathic pulmonary fibrosis and induces myofibroblast differentiation via pH-dependent activation of transforming growth factor-beta","volume":"186","author":"Kottmann","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.bbrc.2011.08.087","article-title":"Extracellular acidification induces connective tissue growth factor production through proton-sensing receptor OGR1 in human airway smooth muscle cells","volume":"413","author":"Matsuzaki","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1254\/jphs.FP0050599","article-title":"Sphingosylphosphorylcholine Antagonizes Proton-Sensing Ovarian Cancer G-Protein-Coupled Receptor 1 (OGR1)-Mediated Inositol Phosphate Production and cAMP Accumulation","volume":"99","author":"Mogi","year":"2005","journal-title":"J. Pharmacol. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/nature15699","article-title":"Allosteric ligands for the pharmacologically dark receptors GPR68 and GPR65","volume":"527","author":"Huang","year":"2015","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1172\/JCI12568","article-title":"Transient expression of IL-1beta induces acute lung injury and chronic repair leading to pulmonary fibrosis","volume":"107","author":"Kolb","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/j.1440-1827.1996.tb03584.x","article-title":"Co-expression of TNF alpha and IL-1 beta in human acute pulmonary fibrotic diseases: An immunohistochemical analysis","volume":"46","author":"Pan","year":"1996","journal-title":"Pathol. Int."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e44","DOI":"10.1164\/rccm.201807-1255ST","article-title":"Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS\/ERS\/JRS\/ALAT Clinical Practice Guideline","volume":"198","author":"Raghu","year":"2018","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.resp.2012.10.003","article-title":"Regulator of G-protein signaling 2 inhibits acid-induced mucin5AC hypersecretion in human airway epithelial cells","volume":"185","author":"Liu","year":"2013","journal-title":"Respir. Physiol. Neurobiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"154","DOI":"10.3389\/fmed.2017.00154","article-title":"Genetics in Idiopathic Pulmonary Fibrosis Pathogenesis, Prognosis, and Treatment","volume":"4","author":"Kaur","year":"2017","journal-title":"Front. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1056\/NEJMoa1103690","article-title":"Efficacy of a Tyrosine Kinase Inhibitor in Idiopathic Pulmonary Fibrosis","volume":"365","author":"Richeldi","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e000397","DOI":"10.1136\/bmjresp-2018-000397","article-title":"Safety and survival data in patients with idiopathic pulmonary fibrosis treated with nintedanib: Pooled data from six clinical trials","volume":"6","author":"Lancaster","year":"2019","journal-title":"BMJ Open Respir. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1124\/mol.117.111062","article-title":"G Protein-Coupled Receptors as Targets for Approved Drugs: How Many Targets and How Many Drugs?","volume":"93","author":"Sriram","year":"2018","journal-title":"Mol. Pharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s11307-014-0784-6","article-title":"Measuring Extracellular pH in a Lung Fibrosis Model with acidoCEST MRI","volume":"17","author":"Jones","year":"2015","journal-title":"Mol. Imaging Biol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/16\/2540\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:10:33Z","timestamp":1760141433000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/16\/2540"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,16]]},"references-count":64,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["cells11162540"],"URL":"https:\/\/doi.org\/10.3390\/cells11162540","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,16]]}}}