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Tubulointerstitial fibrosis of the kidney is also a pathological finding observed in CRD and involves composition of extracellular matrix (ECM). However, an association between these two events has not been elucidated. In this study, we showed that the extracellular\u2010to\u2010intracellular scaffold protein integrin\u2010linked kinase (ILK) regulates expression of tubular water channel aquaporin\u20102 (AQP2) and its apical membrane presence in the renal tubule. Basally, polyuria and decreased urine osmolality were present in ILK conditional\u2010knockdown (cKD\u2010ILK) adult mice compared with nondepleted ILK littermates. No changes were observed in arginine\u2010vasopressin (AVP) blood levels, renal receptor (V2R), or AQP3 expression. However, tubular AQP2 was decreased in expression and apical membrane presence in cKD\u2010ILK mice, where the canonical V2R\/cAMP axis activation is still functional, but independent of the absence of ILK. Thus, cKD\u2010ILK constitutes a nephrogenic diabetes insipidus (NDI) model. AQP2 and ILK colocalize in cultured inner medullary collecting duct (mIMCD3) cells. Specific ILK siRNAs and collagen I (Col) decrease ILK and AQP2 levels and AQP2 presence on the membrane of tubular mIMCD3 cells, which impairs the capacity of the cells to transport water under hypotonic stress. The present work points to ILK as a therapeutic target in NDI.\u2014Cano\u2010Pe\u00f1alver, J. L., Griera, M., Serrano, I., Rodr\u00edguez\u2010Puyol, D., Dedhar, S., de Frutos, S., Rodr\u00edguez\u2010Puyol, M. Integrin\u2010linked kinase regulates tubular aquaporin\u20102 content and intracellular location: a link between the extracellular matrix and water reabsorption.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    28, 3645\u20133659 (2014).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.13-249250","type":"journal-article","created":{"date-parts":[[2014,5,2]],"date-time":"2014-05-02T00:47:57Z","timestamp":1398991677000},"page":"3645-3659","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Integrin\u2010linked kinase regulates tubular aquaporin\u20102 content and intracellular location: a link between the extracellular matrix and water reabsorption"],"prefix":"10.1096","volume":"28","author":[{"given":"Jose Luis","family":"Cano\u2010Pe\u00f1alver","sequence":"first","affiliation":[{"name":"Department of Systems Biology, Physiology Unit Universidad de Alcal\u00e1, Alcal\u00e1 de Henares Madrid Spain"},{"name":"Instituto Reina Sofia de Investigaci\u00f3n Renal Madrid Spain"},{"name":"Red de Investigaci\u00f3n Renal (REDinREN) Instituto de Salud Carlos III Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mercedes","family":"Griera","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, Physiology Unit Universidad de Alcal\u00e1, Alcal\u00e1 de Henares Madrid Spain"},{"name":"Instituto Reina Sofia de Investigaci\u00f3n Renal Madrid Spain"},{"name":"Red de Investigaci\u00f3n Renal (REDinREN) Instituto de Salud Carlos III Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel","family":"Serrano","sequence":"additional","affiliation":[{"name":"Department of Integrative Oncology British Columbia Cancer Research Center Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego","family":"Rodr\u00edguez\u2010Puyol","sequence":"additional","affiliation":[{"name":"Instituto Reina Sofia de Investigaci\u00f3n Renal Madrid Spain"},{"name":"Red de Investigaci\u00f3n Renal (REDinREN) Instituto de Salud Carlos III Madrid Spain"},{"name":"Biomedical Research Foundation Hospital Pr\u00edncipe de Asturias, Alcal\u00e1 de Henares Madrid Spain"},{"name":"Department of Nephrology Hospital Pr\u00edncipe de Asturias, Alcal\u00e1 de Henares Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shoukat","family":"Dedhar","sequence":"additional","affiliation":[{"name":"Department of Integrative Oncology British Columbia Cancer Research Center Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio","family":"de Frutos","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, Physiology Unit Universidad de Alcal\u00e1, Alcal\u00e1 de Henares Madrid Spain"},{"name":"Instituto Reina Sofia de Investigaci\u00f3n Renal Madrid Spain"},{"name":"Red de Investigaci\u00f3n Renal (REDinREN) Instituto de Salud Carlos III Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Rodr\u00edguez\u2010Puyol","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, Physiology Unit Universidad de Alcal\u00e1, Alcal\u00e1 de Henares Madrid Spain"},{"name":"Instituto Reina Sofia de Investigaci\u00f3n Renal Madrid Spain"},{"name":"Red de Investigaci\u00f3n Renal (REDinREN) Instituto de Salud Carlos III Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-012-1129-4"},{"key":"e_1_2_7_3_1","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1254\/jphs.FMJ04004X3","article-title":"Molecular mechanisms and drug development in aquaporin water channel diseases: water channel aquaporin\u20102 of kidney collecting duct cells","volume":"96","author":"Takata K.","year":"2004","journal-title":"J. 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