Effects of simulated bleeding in an in vitro nasal fibroblast wound healing model
We investigated the effect of simulated bleeding on plasminogen activity, matrix metalloproteinase (MMP) expression, and wound healing using a human fibroblast model.
Nasal fibroblasts from three chronic rhinosinusitis (CRS) patients with nasal polyps and three controls were grown in culture and a standardized injury was created using a punch. To mimic bleeding, fibroblasts were stimulated with plasminogen (100 μg/mL), plasminogen + tranexamic acid (TA; 100 μg/mL) or media only. At 24, 48, and 72 hours after injury, we measured urokinase plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) activities and inactive and active MMP-2 and -9 expression.
Injury stimulated the nasal fibroblasts to express uPA and tPA and active and inactive MMP-2 and -9. In CRS patients, plasminogen significantly decreased MMP-9 expression after 48 hours (p < 0.04). In untreated fibroblasts, we observed a decrease in active MMP-9 expression, whereas plasminogen increased active MMP-9 expression after 48 hours (p < 0.04). At 24 hours, active MMP-9 expression was reduced by plasminogen ± TA (p < 0.02). Plasminogen also stimulated uPA expression in CRS patient fibroblasts after 48 hours (p < 0.04). Fibroblast proliferation occurred when exposed to plasminogen and was strongly modulated by uPA and inactive and active MMP-2. The quality of wound healing was affected by inactive MMP-2, uPA and tPA, simulation, and inhibition of bleeding.
Activation of the plasminogen pathway and inactive MMP-2 expression tended to increase both proliferation of nasal fibroblasts and MMP-9 expression as a marker for deterioration of the quality of wound healing.
Document Type: Research Article
Affiliations: Department of Otorhinolaryngology, Head and Neck Surgery, University of Greifswald, Greifswald, Germany; Department of Surgery–Otolaryngology Head and Neck Surgery, The Queen Elizabeth Hospital, Discipline of Surgery, The University of Adelaide, Australia
Publication date: 2010-05-01
- The American Journal of Rhinology & Allergy, is a peer reviewed, scientific publication committed to expanding knowledge and publishing the best clinical and basic research within the fields of Rhinology & Allergy. Its focus is to publish information which contributes to improved quality of care for patients with nasal and sinus disorders. Its primary readership consists of otolaryngologists, allergists, and plastic surgeons. Published material includes peer-reviewed original research, clinical trials and review articles.
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Previously published as American Journal of Rhinology, the journal is indexed in Thomson Reuters Web of Science and Science Citation Index, plus the National Library of Medicine's PubMed service.
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