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Fibroblast Contract...
Fibroblast Contractility in vivo and in vitro : Effects of Prostaglandins and Potential Role for Inner Ear Fluid Homeostasis
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- Hultgård Ekwall, Anna-Karin, 1967- (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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Rubin, Kristofer (preses)
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Rask-Andersen, Helge (preses)
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- Rippe, Bengt, Professor (opponent)
- Institutionen för kliniska vetenskaper, avdelningen för njurmedicin, Universitetssjukhuset i Lund, Lund
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(creator_code:org_t)
- ISBN 9155464327
- Uppsala : Acta Universitatis Upsaliensis, 2005
- Engelska 51 s.
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Serie: Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 1651-6206 ; 96
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Nyckelord
- Biochemistry
- Interstitial connective tissue
- fibroblasts
- prostaglandins
- podoplanin
- endolymph resorption
- Ménière’s disease.
- Biokemi
- Biochemistry
- Biokemi
Publikations- och innehållstyp
- vet (ämneskategori)
- dok (ämneskategori)
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