title: Eotaxin-3 activates the Smad pathway through the transforming growth factor beta 1 in chronic subdural hematoma outer membranes.
abstract: Chronic subdural hematoma (CSDH) is considered to be an inflammatory disease. Eosinophils are frequently expressed in the outer membrane of CSDH and are major sources of transforming growth factor beta (TGF-β). The mothers against decapentaplegic (Smad)-signaling pathway, which is activated by TGF-β, has been shown to be involved with fibrosis. In the present study, we compared the concentrations of eotaxin-3, eosinophil-specific chemoattractant, and TGF-β between CSDH fluid and cerebrospinal fluid (CSF) from control patients. We also explored the expression of the Smad-signaling pathway in the outer membrane of CSDH. Eight patients whose outer membrane and 12 whose CSDH fluid were successfully obtained during trepanation surgery were included in the study. Concentrations of eotaxin-3 and TGF-β were measured by enzyme immunoassay kits. Expression levels of Smad2, phosphorylated Smad3, Smad3, Smad4, and actin were examined by Western blot analysis. In addition, expression of Smad3 was also examined by immunohistochemistry. Concentrations of eotaxin-3 and TGF-β in CSDH fluid were significantly higher than those in CSF. Smad2, Smad3, phosphorylated Smad3, and Smad4 were detected in all cases. Smad3 was shown to be present in fibroblasts. These findings indicate that eotaxin-3 is expressed in CSDH fluid, inducing eosinophils into the outer membrane and resulting in elevation of TGF-β with the Smad pathway activated by TGF-β. These data suggest a potential mechanism for CSDH formation and growth.
authors.affiliation: 1 Department of Neurological Surgery, Aichi Medical University , Aichi, Japan .
authors.forename: Koji
authors.initials: K
authors.lastname: Osuka
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Nobuteru
authors.initials: N
authors.lastname: Usuda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Aoyama
authors.forename: Mikinobu
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Masakazu
authors.initials: M
authors.lastname: Takayasu
mesh_terms: D000368:Aged; D015153:Blotting, Western; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020200:Hematoma, Subdural, Chronic / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction / Q000502:physiology*; D051785:Smad Proteins / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: C120429:CCL26 protein, human; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1
keywords: Smad; TGF-β; chronic subdural hematoma; eosinophils; eotaxin-3