{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:14:35Z","timestamp":1790813675397,"version":"4.1.0"},"reference-count":86,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2017,10,1]]},"abstract":"<jats:p>The renal collecting duct (CD) contains two major cell types, intercalated (ICs) and principal cells (PCs). A previous report showed that deletion of \u03b21-integrin in the entire renal CD causes defective CD morphogenesis resulting in kidney dysfunction. However, subsequent deletion of \u03b21-integrin specifically in ICs and PCs, respectively, did not cause any morphological defects in the CDs. The discrepancy between these studies prompts us to reinvestigate the role of \u03b21-integrin in CD cells, specifically in the PCs. We conditionally deleted \u03b21-integrin in mouse CD PCs using a specific aquaporin-2 (AQP2) promoter Cre-LoxP system. The resulting mutant mice, \u03b2-1<jats:sup>f\/f<\/jats:sup>AQP2-Cre+, had lower body weight, failed to thrive, and died around 8\u201312 wk. Their CD tubules were dilated, and some of them contained cellular debris. Increased apoptosis and proliferation of PCs were observed in the dilated CDs. Trichrome staining and electron microscopy revealed the presence of peritubular and interstitial fibrosis that is associated with increased production of extracellular matrix proteins including collagen type IV and fibronectin, as detected by immunoblotting. Further analysis revealed a significantly increased expression of transforming growth factor-\u03b2 (TGF-\u03b2)-induced protein, fibronectin, and TGF-\u03b2 receptor-1 mRNAs and concomitantly increased phosphorylation of SMAD-2 that indicates the activation of the TGF-\u03b2 signaling pathway. Therefore, our data reveal that normal expression of \u03b21-integrin in PCs is a critical determinant of CD structural and functional integrity and further support the previously reported critical role of \u03b21-integrin in the development and\/or maintenance of the CD structure and function.<\/jats:p>","DOI":"10.1152\/ajprenal.00038.2017","type":"journal-article","created":{"date-parts":[[2017,7,13]],"date-time":"2017-07-13T00:25:26Z","timestamp":1499905526000},"page":"F1026-F1037","source":"Crossref","is-referenced-by-count":25,"title":["Deletion of \u03b21-integrin in collecting duct principal cells leads to tubular injury and renal medullary fibrosis"],"prefix":"10.1152","volume":"313","author":[{"given":"Fahmy A.","family":"Mamuya","sequence":"first","affiliation":[{"name":"Program in Membrane Biology and Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts;"},{"name":"Center for Systems Biology, Massachusetts General Hospital, Boston, Massachusetts;"},{"name":"Harvard Medical School, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongping","family":"Xie","sequence":"additional","affiliation":[{"name":"Program in Membrane Biology and Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts;"},{"name":"Center for Systems Biology, Massachusetts General Hospital, Boston, Massachusetts;"},{"name":"Harvard Medical School, Boston, Massachusetts;"},{"name":"Department of Physiology, Tongji University School of Medicine, Shanghai, China; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Lei","sequence":"additional","affiliation":[{"name":"Program in Membrane Biology and Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts;"},{"name":"Center for Systems Biology, Massachusetts General Hospital, Boston, Massachusetts;"},{"name":"Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Huang","sequence":"additional","affiliation":[{"name":"Program in Membrane Biology and Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts;"},{"name":"Center for Systems Biology, Massachusetts General Hospital, Boston, Massachusetts;"},{"name":"Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Tsuji","sequence":"additional","affiliation":[{"name":"Program in Membrane Biology and Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts;"},{"name":"Center for Systems Biology, Massachusetts General Hospital, Boston, Massachusetts;"},{"name":"Harvard Medical School, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane E.","family":"Capen","sequence":"additional","affiliation":[{"name":"Program in Membrane Biology and Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts;"},{"name":"Center for Systems Biology, Massachusetts General Hospital, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"BaoXue","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph","family":"Weissleder","sequence":"additional","affiliation":[{"name":"Center for Systems Biology, Massachusetts General Hospital, Boston, Massachusetts;"},{"name":"Harvard Medical School, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teodor G.","family":"P\u0103unescu","sequence":"additional","affiliation":[{"name":"Program in Membrane Biology and Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts;"},{"name":"Center for Systems Biology, Massachusetts General Hospital, Boston, Massachusetts;"},{"name":"Harvard Medical School, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua A. 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