{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:52Z","timestamp":1787028532961,"version":"build-2736575974"},"reference-count":52,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T00:00:00Z","timestamp":1707091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CounterACT Program","award":["UO1ES030674"],"award-info":[{"award-number":["UO1ES030674"]}]},{"name":"National Institutes of Health Office of the Director (NIH OD)","award":["UO1ES030674"],"award-info":[{"award-number":["UO1ES030674"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UO1ES030674"],"award-info":[{"award-number":["UO1ES030674"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Exposure to hydrochloric acid (HCl) can provoke acute and chronic lung injury. Because of its extensive production for industrial use, frequent accidental exposures occur, making HCl one of the top five chemicals causing inhalation injuries. There are no Food and Drug Administration (FDA)-approved treatments for HCl exposure. Heat shock protein 90 (HSP90) inhibitors modulate transforming growth factor-\u03b2 (TGF-\u03b2) signaling and the development of chemical-induced pulmonary fibrosis. However, little is known on the role of Heat Shock Protein 70 (HSP70) during injury and treatment with HSP90 inhibitors. We hypothesized that administration of geranylgeranyl-acetone (GGA), an HSP70 inducer, or gefitinib (GFT), an HSP70 suppressant, alone or in combination with the HSP90 inhibitor, TAS-116, would improve or worsen, respectively, HCl-induced chronic lung injury in vivo and endothelial barrier dysfunction in vitro. GGA, alone, improved HCl-induced human lung microvascular endothelial cells (HLMVEC) barrier dysfunction and, in combination with TAS-116, improved the protective effect of TAS-116. In mice, GGA reduced HCl toxicity and while TAS-116 alone blocked HCl-induced chronic lung injury, co-administration with GGA, resulted in further improvement. Conversely, GFT potentiated HCl-induced barrier dysfunction and impaired the antidotal effects of TAS-116. We conclude that combined treatments with HSP90 inhibitors and HSP70 inducers may represent a novel therapeutic approach to manage HCl-induced chronic lung injury and pulmonary fibrosis.<\/jats:p>","DOI":"10.3390\/ijms25031920","type":"journal-article","created":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T05:22:44Z","timestamp":1707110564000},"page":"1920","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["HSP70 Is a Critical Regulator of HSP90 Inhibitor\u2019s Effectiveness in Preventing HCl-Induced Chronic Lung Injury and Pulmonary Fibrosis"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1174-3876","authenticated-orcid":false,"given":"Ruben M. L.","family":"Colunga Biancatelli","sequence":"first","affiliation":[{"name":"Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA 23509, USA"},{"name":"Division of Pulmonary and Critical Care, Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA 23507, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1705-027X","authenticated-orcid":false,"given":"Pavel A.","family":"Solopov","sequence":"additional","affiliation":[{"name":"Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA 23509, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tierney","family":"Day","sequence":"additional","affiliation":[{"name":"Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA 23509, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betsy","family":"Gregory","sequence":"additional","affiliation":[{"name":"Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA 23509, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Osei-nkansah","sequence":"additional","affiliation":[{"name":"Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA 23509, USA"},{"name":"School of Medicine, Eastern Virginia Medical School, Norfolk, VA 23507, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiana","family":"Dimitropoulou","sequence":"additional","affiliation":[{"name":"Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA 23509, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5098-295X","authenticated-orcid":false,"given":"John D.","family":"Catravas","sequence":"additional","affiliation":[{"name":"Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA 23509, USA"},{"name":"Division of Pulmonary and Critical Care, Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA 23507, USA"},{"name":"School of Medical Diagnostic & Translational Sciences, College of Health Sciences, Old Dominion University, Norfolk, VA 23509, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,5]]},"reference":[{"key":"ref_1","first-page":"39","article-title":"Top five chemicals resulting in injuries from acute chemical incidents\u2014Hazardous Substances Emergency Events Surveillance, nine states, 1999\u20132008","volume":"64","author":"Anderson","year":"2015","journal-title":"MMWR Suppl."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.toxlet.2019.12.005","article-title":"Choking agents and chlorine gas\u2014History, pathophysiology, clinical effects and treatment","volume":"320","author":"Zellner","year":"2020","journal-title":"Toxicol. 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