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This effect was independent of hypoxia\u2010induced contractility which was ROCK\u2010dependent rather than HSP27\u2010dependent. Results described here show that increased HSP27 phosphorylation not only does not underlie hypoxia\u2010induced permeability, but may actually augment the endothelial barrier. Hypoxia causes gap formation between RPMEC and increases MLC2 phosphorylation. The phosphorylation of MYPT1, which inhibits MLC2 phosphatase, is also increased in hypoxia. In addition, FAK phosphorylation, which alters focal adhesion signaling, is increased in hypoxia. Overexpressing phosphomimicking HSP27 (pmHSP27), which induces significant actin stress fiber formation, surprisingly renders RPMEC resistant to hypoxia\u2010 or TGF\u03b2\u2010induced permeability. siRNA against pmHSP27 reverses the increased actin stress fiber formation in pmHSP27\u2010overexpressing cells, and disrupting actin stress fibers in pmHSP27\u2010overexpressing RPMEC renders them more susceptible to hypoxia. Finally, hypoxia\u2010induced gap formation, as well as phosphorylation of MLC2, MYPT1 and FAK are almost abolished by overexpressing pmHSP27 in RPMEC. These effects of pmHSP27 overexpression might represent decreased cytoskeletal plasticity and increased tethering which counteracts permeability\u2010inducing contractility. Thus hypoxia activates two pathways one leading to contractility and increased permeability, the other leading to actin stress fibers, stronger adhesion, and reduced permeability. Altering HSP27 phosphorylation, which tips the balance towards decreased permeability, might be targeted in managing endothelial barrier dysfunction. J. Cell. Physiol. 220: 600\u2013610, 2009. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.21773","type":"journal-article","created":{"date-parts":[[2009,4,16]],"date-time":"2009-04-16T15:54:20Z","timestamp":1239897260000},"page":"600-610","source":"Crossref","is-referenced-by-count":28,"title":["Modulation of HSP27 alters hypoxia\u2010induced endothelial permeability and related signaling pathways"],"prefix":"10.1002","volume":"220","author":[{"given":"Tiegang","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oscar E.","family":"Guevara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rod R.","family":"Warburton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas 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