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An interstitial network of podoplanin-expressing cells in the human endolymphatic duct
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
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2006 (English)In: Journal of the Association for Research in Otolaryngology, ISSN 1525-3961, E-ISSN 1438-7573, Vol. 7, no 1, 38-47 p.Article in journal (Refereed) Published
Abstract [en]

The human endolymphatic duct (ED) with encompassing interstitial connective tissue (CT) is believed to be important for endolymph resorption and fluid pressure regulation of the inner ear. The periductal CT cells are interconnected via numerous cellular extensions, but do not form vessel structures. Here we report that the periductal CT is populated by two distinct cell phenotypes; one expressing podoplanin, a protein otherwise found on lymph endothelia and on epithelia involved in fluid fluxes, and a second expressing a fibroblast marker. A majority of the interstitial cells expressed podoplanin but not the lymphatic endothelial cell markers hyaluronan receptor (LYVE-1) or vascular endothelial growth factor receptor-3 (VEGFR-3). The fibroblast marker positive cells were found close to the ED epithelium. In the mid- and distal parts of the ED, these cells were enriched under folded epithelia. Furthermore, subepithelial CT cells were found to express activated platelet derived growth factor (PDGF)-beta receptors. Cultured CT cells from human inner ear periductal and perisaccular explant tissues were identified as fibroblasts. These cells compacted a three-dimensional collagen lattice by a process that could be promoted by PDGF-BB, a factor involved in interstitial fluid pressure regulation. Our results are compatible with the notion that the periductal CT cells are involved in the regulation of inner ear fluid pressure. By active compaction of the periductal CT and by the formation of villous structures, the CT cells could modulate fluid fluxes over the ED epithelium as well as the longitudinal flow of endolymph in the ED.

Place, publisher, year, edition, pages
2006. Vol. 7, no 1, 38-47 p.
Keyword [en]
Biological Markers/analysis, Connective Tissue/pathology/physiopathology/ultrastructure, Endolymphatic Duct/*pathology/*physiopathology/surgery/ultrastructure, Fibroblasts/cytology/physiology, Humans, Immunohistochemistry, Male, Membrane Glycoproteins/*metabolism, Neurilemmoma/surgery, Organ Culture Techniques, Penis, Skin Physiology
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-22531DOI: 10.1007/s10162-005-0021-8PubMedID: 16408168OAI: oai:DiVA.org:uu-22531DiVA: diva2:50304
Available from: 2007-05-04 Created: 2007-05-04 Last updated: 2013-09-13Bibliographically approved
In thesis
1. Fibroblast Contractility in vivo and in vitro: Effects of Prostaglandins and Potential Role for Inner Ear Fluid Homeostasis
Open this publication in new window or tab >>Fibroblast Contractility in vivo and in vitro: Effects of Prostaglandins and Potential Role for Inner Ear Fluid Homeostasis
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Fibroblasts continuously strive to organize and compact the surrounding extracellular matrix (ECM). Recent data suggest that this cellular contractility controls interstitial fluid homeostasis in loose connective tissues (CT). The aim of this thesis was to study the effects of prostaglandins on fibroblast contractility and to investigate whether fibroblasts in the interstitial CT surrounding the human endolymphatic duct (ED) can modulate inner ear fluid pressure and endolymph resorption.

Paper I shows that prostaglandin E1 (PGE1) and prostacyclin inhibit fibroblast-mediated collagen matrix compaction in vitro and lower the interstitial fluid pressure in vivo in rat dermis. Paper II demonstrates that the inhibition of collagen matrix compaction by PGE1 is protein kinase A-dependent. Furthermore, PGE1 induces a complete but reversible actin depolymerization in human dermal fibroblasts by affecting the phosphorylation state of regulatory actin-binding proteins. Paper III describes that the cells of the interstitial CT encompassing the human ED are organized in a network based on intercellular- and cell-ECM contacts. Paper IV shows that two distinct cell phenotypes populate this interstitial CT: one expressing the lymph endothelial marker podoplanin and the other a fibroblast marker. Furthermore, CT cells isolated from human ED tissues exhibited the same tissue compacting properties in vitro as dermal fibroblasts.

In conclusion, PGE1 inhibits fibroblast contractility by interfering with the stability and dynamics of the actin cytoskeleton, which leads to a loss of integrin-mediated adhesion to the ECM. These mechanisms are supposedly involved in edema formation in skin during inflammation and might be involved in the formation of endolymphatic hydrops in the inner ear of patients with Ménière’s disease.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2005. 51 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 96
Biochemistry, Interstitial connective tissue, fibroblasts, prostaglandins, podoplanin, endolymph resorption, Ménière’s disease., Biokemi
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
urn:nbn:se:uu:diva-6259 (URN)91-554-6432-7 (ISBN)
Public defence
2006-01-20, Rudbecksalen, Rudbecklaboratoriet, Uppsala, 13:15
Available from: 2005-12-30 Created: 2005-12-30 Last updated: 2013-09-13Bibliographically approved

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