{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T04:37:38Z","timestamp":1790311058809,"version":"4.1.0"},"reference-count":51,"publisher":"National Academy of Sciences","issue":"36","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2014,9,9]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>How the kidney handles chloride reabsorption has long been a mystery. Here, we have discovered a pathway in the kidney that utilizes channel-activating protease 1 and claudin-4 to physiologically regulate tight junction permeability to chloride. Such a pathway not only is important in renal regulation of chloride but also may play key roles in chloride transport across many other epithelia such as the lung, the salivary gland, and the skin. This discovery also attests to a concept of \u201cdruggable\u201d tight junction. Proteases or protease-dependent mechanisms may be developed as pharmacological tools to transiently regulate tight junction permeability in the kidney, the intestine, and the blood\u2013brain barrier.<\/jats:p>","DOI":"10.1073\/pnas.1406741111","type":"journal-article","created":{"date-parts":[[2014,8,25]],"date-time":"2014-08-25T23:20:35Z","timestamp":1409008835000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":65,"title":["The Cap1\u2013claudin-4 regulatory pathway is important for renal chloride reabsorption and blood pressure regulation"],"prefix":"10.1073","volume":"111","author":[{"given":"Yongfeng","family":"Gong","sequence":"first","affiliation":[{"name":"Department of Internal Medicine\u2013Renal Division,"},{"name":"Center for Investigation of Membrane Excitability Diseases, and"},{"name":"Department of Physiology, Binzhou Medical College, Yantai 264003, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Tulane University Health Science Center, New Orleans, LA 70112; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine\u2013Renal Division,"},{"name":"Center for Investigation of Membrane Excitability Diseases, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernie","family":"Gonzales","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University Medical School, St Louis, MO 63110;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronaldo","family":"Perez","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University Medical School, St Louis, MO 63110;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingli","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piyush","family":"Tripathi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine\u2013Renal Division,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen S.","family":"Hering-Smith","sequence":"additional","affiliation":[{"name":"Department of Medicine, Tulane University Health Science Center, New Orleans, LA 70112; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. Lee","family":"Hamm","sequence":"additional","affiliation":[{"name":"Department of Medicine, Tulane University Health Science Center, New Orleans, LA 70112; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianghui","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine\u2013Renal Division,"},{"name":"Center for Investigation of Membrane Excitability Diseases, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2014,8,25]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6648527"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6322303"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2063193"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00241-0"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2000.80.1.277"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.071516798"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI40145"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/367463a0"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00155.2007"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2009121257"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1009399107"},{"key":"e_1_3_3_12_2","first-page":"F291","article-title":"Microelectrode assessment of chloride-conductive properties of cortical collecting duct","volume":"247","author":"Sansom SC","year":"1984","unstructured":"SC Sansom, EJ Weinman, RG O\u2019Neil, Microelectrode assessment of chloride-conductive properties of cortical collecting duct. Am J Physiol 247, F291\u2013F302 (1984).","journal-title":"Am J Physiol"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-030212-183705"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/39329"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.20028598"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200213229"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200110122"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.136.6.1239"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00299.2010"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052272"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.24.11663"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2009101077"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2006090975"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-201X.2004.01315.x"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000013055.48885.8D"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V115828"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02631"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-009-0307-y"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00637.2005"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1998.274.6.C1429"},{"key":"e_1_3_3_31_2","first-page":"619","article-title":"Claudin-16 and claudin-19 interact and form a cation-selective tight junction complex","volume":"118","author":"Hou J","year":"2008","unstructured":"J Hou, et al., Claudin-16 and claudin-19 interact and form a cation-selective tight junction complex. J Clin Invest 118, 619\u2013628 (2008).","journal-title":"J Clin Invest"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0907724106"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.147.4.891"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M703547200"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.07-8319com"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI26323"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.09.123"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2283"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1006128107"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2061"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.1991.tb01370.x"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V112369"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0611727104"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0406172101"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00314.2005"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00096.2009"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.443432"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0903923107"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200501038"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-012110-142150"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.312165"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1406741111","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T22:37:49Z","timestamp":1649803069000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1406741111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,8,25]]},"references-count":51,"journal-issue":{"issue":"36","published-print":{"date-parts":[[2014,9,9]]}},"alternative-id":["10.1073\/pnas.1406741111"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1406741111","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718544552.793502195","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,8,25]]},"assertion":[{"value":"2014-08-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}