title: Claudin expression in the rat endolymphatic duct and sac - first insights into regulation of the paracellular barrier by vasopressin.
abstract: Hearing and balance functions of the inner ear rely on the homeostasis of the endolymphatic fluid. When disturbed, pathologic endolymphatic hydrops evolves as observed in Menière's disease. The molecular basis of inner ear fluid regulation across the endolymphatic epithelium is largely unknown. In this study we identified the specific expression of the tight junction (TJ) molecules Claudin 3, 4, 6, 7, 8, 10, and 16 in epithelial preparations of the rat inner ear endolymphatic duct (ED) and endolymphatic sac (ES) by high-throughput qPCR and immunofluorescence confocal microscopy. Further we showed that Claudin 4 in the ES is a target of arginine-vasopressin (AVP), a hormone elevated in Menière's disease. Moreover, our transmission-electron microscopy (TEM) analysis revealed that the TJs of the ED were shallow and shorter compared to the TJ of the ES indicating facilitation of a paracellular fluid transport across the ED epithelium. The significant differences in the subcellular localization of the barrier-forming protein Claudin 3 between the ED and ES epithelium further support the TEM observations. Our results indicate a high relevance of Claudin 3 and Claudin 4 as important paracellular barrier molecules in the ED and ES epithelium with potential involvement in the pathophysiology of Menière's disease.
authors.affiliation: Institute of Clinical Anatomy and Cell Analysis, University of Tübingen, Tübingen, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Runggaldier
authors.affiliation: Institute of Clinical Anatomy and Cell Analysis, University of Tübingen, Tübingen, Germany.
authors.forename: Lidia Garcia
authors.initials: LG
authors.lastname: Pradas
authors.affiliation: Institute of Clinical Anatomy and Cell Analysis, University of Tübingen, Tübingen, Germany.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Neckel
authors.affiliation: Institute of Clinical Anatomy and Cell Analysis, University of Tübingen, Tübingen, Germany.
authors.forename: Andreas F
authors.initials: AF
authors.lastname: Mack
authors.affiliation: Institute of Clinical Anatomy and Cell Analysis, University of Tübingen, Tübingen, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hirt
authors.affiliation: Institute of Clinical Anatomy and Cell Analysis, University of Tübingen, Tübingen, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Gleiser
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects*; D057167:Claudins / Q000235:genetics / Q000378:metabolism*; D004711:Endolymphatic Duct / Q000378:metabolism*; D004712:Endolymphatic Sac / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008575:Meniere Disease / Q000378:metabolism / Q000473:pathology; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019108:Tight Junctions / Q000502:physiology / Q000648:ultrastructure
chemical_list: D057167:Claudins; D020033:Protein Isoforms; D012333:RNA, Messenger; D001127:Arginine Vasopressin