{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T18:09:43Z","timestamp":1782238183176,"version":"3.54.5"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2008,11,1]],"date-time":"2008-11-01T00:00:00Z","timestamp":1225497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Heat shock protein 90 (hsp90) inhibitors inactivate and\/or degrade various client proteins, including many involved in inflammation. Increased vascular permeability is a hallmark of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Thus, we tested the hypothesis that hsp90 inhibitors may prevent and\/or restore endothelial cell (EC) permeability after injury. Exposure of confluent bovine pulmonary arterial endothelial cell (BPAEC) monolayer to TGF-\u03b21, thrombin, bacterial lipopolysaccharide (LPS), or vascular endothelial growth factor (VEGF) increased BPAEC permeability, as revealed by decreased transendothelial electrical resistance (TER). Treatment of injured endothelium with hsp90 inhibitors completely restored TER of BPAEC. Similarly, preincubation of BPAEC with hsp90 inhibitors prevented the decline in TER induced by the exposure to thrombin, LPS, VEGF, or TGF-\u03b21. In addition, hsp90 inhibitors restored the EC barrier function after PMA or nocodazole-induced hyperpermeability. These effects of the hsp90 inhibitors were associated with the restoration of TGF-\u03b21\u2013 or nocodazole-induced decrease in VE-cadherin and \u03b2-catenin expression at EC junctions. The protective effect of hsp90 inhibitors on TGF-\u03b21\u2013induced hyperpermeability was critically dependent upon preservation of F-actin cytoskeleton and was associated with the inhibition of agonist-induced myosin light chain (MLC) and myosin phosphatase target subunit 1 (MYPT1) phosphorylation, F-actin stress fibers formation, microtubule disassembly, increase in hsp27 phosphorylation, and association of hsp90 with hsp27, but independent of p38MAPK activity. We conclude that hsp90 inhibitors exert barrier protective effects on BPAEC, at least in part, via inhibition of hsp27-mediated, agonist-induced cytoskeletal rearrangement, and therefore may have useful therapeutic value in ALI, ARDS, and other pulmonary inflammatory disease.<\/jats:p>","DOI":"10.1165\/rcmb.2007-0324oc","type":"journal-article","created":{"date-parts":[[2008,5,12]],"date-time":"2008-05-12T20:53:35Z","timestamp":1210625615000},"page":"551-559","source":"Crossref","is-referenced-by-count":72,"title":["Heat Shock Protein 90 Inhibitors Protect and Restore Pulmonary Endothelial Barrier Function"],"prefix":"10.1093","volume":"39","author":[{"given":"Alexander","family":"Antonov","sequence":"first","affiliation":[{"name":"Pulmonary Vascular Disease Program, Vascular Biology Center"},{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connie","family":"Snead","sequence":"additional","affiliation":[{"name":"Pulmonary Vascular Disease Program, Vascular Biology Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Gorshkov","sequence":"additional","affiliation":[{"name":"Pulmonary Vascular Disease Program, Vascular Biology Center"},{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galina N.","family":"Antonova","sequence":"additional","affiliation":[{"name":"Pulmonary Vascular Disease Program, Vascular Biology Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander D.","family":"Verin","sequence":"additional","affiliation":[{"name":"Pulmonary Vascular Disease Program, Vascular Biology Center"},{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, 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