title: Expression of large tenascin-C splice variants by hepatic stellate cells/myofibroblasts in chronic hepatitis C.
abstract: OBJECTIVE
  Earlier studies have suggested involvement of tenascin-C (TN-C) in liver fibrosis. Here, we examined expression of TN-C variants and types of alternatively spliced fibronectin-type III (FNIII) repeats in chronic hepatitis.
  
  
  METHODS
  Using three monoclonal antibodies against TN-C variants, immunohistochemical staining was performed and the correlation with histological parameters of chronic hepatitis C was examined. The cellular source was also determined and variant expression and their types were tested using isolated rat hepatic stellate cells (HSCs), liver myofibroblasts, and/or LI90 cells.
  
  
  RESULTS
  Large variants were not expressed in normal liver, but were up-regulated in chronic hepatitis, especially at sites of interface hepatitis and confluent necrosis, showing stronger correlations between staining intensity and these than with other parameters or fibrosis. TN-C deposition was closely correlated with increase in the number of alpha-smooth muscle actin-positive cells, i.e. activated HSCs/myofibroblasts, and in situ hybridization showed TN-C mRNA signals in the cells. Activated HSCs and myofibroblasts in culture highly expressed large variants of TN-C. In LI90 cells, sequencing of large variants revealed that the FNIII repeats D and A1/A4, followed by B, were preferentially included.
  
  
  CONCLUSIONS
  TN-C and its variants are produced by HSCs/myofibroblasts, suggesting important roles in liver fibrogenesis.
authors.affiliation: Department of Pathology and Matrix Biology, Mie University Graduate School of Medicine, Mie, Japan.
authors.forename: Amro
authors.initials: A
authors.lastname: El-Karef
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kaito
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ikeda
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nishioka
authors.forename: Naoki
authors.initials: N
authors.lastname: Fujita
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Inada
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Adachi
authors.forename: Norifumi
authors.initials: N
authors.lastname: Kawada
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakajima
authors.forename: Kyoko
authors.initials: K
authors.lastname: Imanaka-Yoshida
authors.forename: Toshimichi
authors.initials: T
authors.lastname: Yoshida
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D017398:Alternative Splicing; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002478:Cells, Cultured; D002908:Chronic Disease; D018604:Epitope Mapping; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D014644:Genetic Variation; D006505:Hepatitis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling; D019063:Tenascin / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*
chemical_list: D000199:Actins; D000911:Antibodies, Monoclonal; D019063:Tenascin