title: Tenascin-C triggers fibrin accumulation by downregulation of tissue plasminogen activator.
abstract: We explored novel functions of tenascin-C by comparing mouse embryonic fibroblasts (MEFs) proficient or deficient in tenascin-C expression. Transcript profiling analysis identified tissue plasminogen activator (tPA) as the most consistently over-expressed gene in all tenascin-C deficient MEFs. This was confirmed by real-time PCR as well as by protein expression analysis. In agreement with these observations, tenascin-C deficient MEFs had an increased capacity to digest fibrin in situ. Consistently, tenascin-C expression in vivo was found to correlate with fibrin deposition in several diseases associated with tenascin-C overexpression such as fibrosis, asthma and cancer. In conclusion, the present study suggests a new role of tenascin-C as a regulator of the fibrinolytic system.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, Basel, Switzerland. florence.brellier@fmi.ch
authors.forename: Florence
authors.initials: F
authors.lastname: Brellier
authors.forename: Katrin
authors.initials: K
authors.lastname: Hostettler
authors.forename: Hans-Rudolf
authors.initials: HR
authors.lastname: Hotz
authors.forename: Ceyda
authors.initials: C
authors.lastname: Ozcakir
authors.forename: Sedat A
authors.initials: SA
authors.lastname: Çöloğlu
authors.forename: Dieudonnée
authors.initials: D
authors.lastname: Togbe
authors.forename: Bernard
authors.initials: B
authors.lastname: Ryffel
authors.forename: Michael
authors.initials: M
authors.lastname: Roth
authors.forename: Ruth
authors.initials: R
authors.lastname: Chiquet-Ehrismann
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D004622:Embryo, Mammalian / Q000166:cytology; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D005341:Fibrinolysin / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D020869:Gene Expression Profiling; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008171:Lung Diseases / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019063:Tenascin / Q000235:genetics / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000378:metabolism*
chemical_list: D019063:Tenascin; D005337:Fibrin; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin