{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T02:55:57Z","timestamp":1767840957740,"version":"3.49.0"},"reference-count":84,"publisher":"American Physiological Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2014,10,15]]},"abstract":"<jats:p>Epithelial sodium channels (ENaC) govern transepithelial salt and fluid homeostasis. ENaC contributes to polarization, apoptosis, epithelial-mesenchymal transformation, etc. Fibrinolytic proteases play a crucial role in virtually all of these processes and are elaborated by the airway epithelium. We hypothesized that urokinase-like plasminogen activator (uPA) regulates ENaC function in airway epithelial cells and tested that possibility in primary murine tracheal epithelial cells (MTE). Both basal and cAMP-activated Na<jats:sup>+<\/jats:sup>flow through ENaC were significantly reduced in monolayers of uPA-deficient cells. The reduction in ENaC activity was further confirmed in basolateral membrane-permeabilized cells. A decrease in the Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-ATPase activity in the basolateral membrane could contribute to the attenuation of ENaC function in intact monolayer cells. Dysfunctional fluid resolution was seen in uPA-disrupted cells. Administration of uPA and plasmin partially restores ENaC activity and fluid reabsorption by MTEs. ERK1\/2, but not Akt, phosphorylation was observed in the cells and lungs of uPA-deficient mice. On the other hand, cleavage of \u03b3 ENaC is significantly depressed in the lungs of uPA knockout mice vs. those of wild-type controls. Expression of caspase 8, however, did not differ between wild-type and uPA<jats:sup>\u2212\/\u2212<\/jats:sup>mice. In addition, uPA deficiency did not alter transepithelial resistance. Taken together, the mechanisms for the regulation of ENaC by uPA in MTEs include augmentation of Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-ATPase, proteolysis, and restriction of ERK1\/2 phosphorylation. We demonstrate for the first time that ENaC may serve as a downstream signaling target by which uPA controls the biophysical profiles of airway fluid and epithelial function.<\/jats:p>","DOI":"10.1152\/ajplung.00126.2014","type":"journal-article","created":{"date-parts":[[2014,8,30]],"date-time":"2014-08-30T01:02:53Z","timestamp":1409360573000},"page":"L609-L617","source":"Crossref","is-referenced-by-count":26,"title":["Regulation of epithelial sodium channels in urokinase plasminogen activator deficiency"],"prefix":"10.1152","volume":"307","author":[{"given":"Zaixing","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas;"},{"name":"School of Pharmacy, China Medical University, Liaoning Shenyang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Runzhen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meimi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas;"},{"name":"School of Pharmacy, China Medical University, Liaoning Shenyang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinrong","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deepa","family":"Bhattarai","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rohan","family":"Dhiman","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Immunology, The University of Texas Health Science Center at Tyler, Tyler, Texas;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sreerama","family":"Shetty","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Idell","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas;"},{"name":"Department of Medicine, The University of Texas Health Science Center at Tyler, Tyler, Texas;"},{"name":"Texas Lung Injury Institute, The University of Texas Health Science Center at Tyler, Tyler, Texas; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong-Long","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas;"},{"name":"Texas Lung Injury Institute, The University of Texas Health Science Center at Tyler, Tyler, Texas; and"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1999.277.1.F121"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1348-0421.2001.tb01291.x"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00390.2004"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119089"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1172\/JCI3971"},{"key":"B6","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1128\/IAI.67.2.879-884.1999","volume":"67","author":"Beck JM","year":"1999","journal-title":"Infect Immun"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.00631.x"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199003293221304"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00373.2002"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.162933"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M610636200"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/367463a0"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2008-0034OC"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8858"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2005.09.050"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-1388"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1513\/pats.2306008"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.066704"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00178.2005"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.200810030"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.2.801"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201110763"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-11-65"},{"key":"B24","first-page":"227","volume":"23","author":"Hildenbrand R","year":"2008","journal-title":"Histol Histopathol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.240861"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307003200"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/ng0396-325"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1159\/000272051"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000057846.21303.AB"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.2309012"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/144.1.187"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114217"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200204-313OC"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2001.281.1.C64"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00259.2011"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00007.2002"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R800083200"},{"key":"B38","first-page":"524","volume":"19","author":"Kleyman TR","year":"1999","journal-title":"Semin Nephrol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/0300-483X(90)90159-E"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.90434.2008"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1998.274.6.L1040"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.157.2.9707052"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2011-0309OC"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00094.2011"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M701923200"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(93)81336-X"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/nm1028"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.151803"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200708-1233OC"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01241.2001"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.61.1.627"},{"key":"B52","first-page":"43","volume":"16","author":"Matsuo O","year":"1986","journal-title":"Haemostasis"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00003.2002"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201001-0074UP"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1995.268.5.C1157"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2011.03.004"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2009.170324"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2008-0166OC"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2004-0162OC"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M805676200"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/S0070-2153(06)78002-4"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00312.2002"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-06-164210"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00307.2007"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.131078"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.64.082101.143243"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.010908.163108"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1160\/TH08-03-0142"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.2001.280.4.L792"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00439.2005"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2011-0390OC"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1021\/bi201293x"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00049.2002"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2821"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M407858200"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00031.2011"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.22.14037"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00321.2009"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M505832200"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M401004200"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2008.07.018"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2012.251"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M512046200"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00331.2011"}],"container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajplung.00126.2014","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,8,23]],"date-time":"2020-08-23T22:19:17Z","timestamp":1598221157000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajplung.00126.2014"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,10,15]]},"references-count":84,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2014,10,15]]}},"alternative-id":["10.1152\/ajplung.00126.2014"],"URL":"https:\/\/doi.org\/10.1152\/ajplung.00126.2014","relation":{},"ISSN":["1040-0605","1522-1504"],"issn-type":[{"value":"1040-0605","type":"print"},{"value":"1522-1504","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10,15]]}}}