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Prostaglandin E1 stimulates phosphorylation of caldesmon and depolymerizes F-actin in a cAMP- and PKA dependent manner in human dermal fibroblasts
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
(English)Manuscript (Other academic)
URN: urn:nbn:se:uu:diva-93900OAI: oai:DiVA.org:uu-93900DiVA: diva2:167536
Available from: 2005-12-30 Created: 2005-12-30 Last updated: 2011-06-28Bibliographically 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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Rubin, Kristofer
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