BACKGROUND/AIMS: 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.
BACKGROUND/AIMS: 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: Akif Altinbas; Jacinta A Holmes; Shadi Salloum; Anna Lidofsky; Nadia Alatrakchi; Ma Somsouk; Peter Hunt; Steven Deeks; Kara W Chew; Georg Lauer; Annie Kruger; Wenyu Lin; Raymond T Chung Journal: Biomark Med Date: 2022-07-05 Impact factor: 2.498
Authors: Jennifer H Benbow; April D Elam; Krista L Bossi; Danae L Massengill; Elizabeth Brandon-Warner; William E Anderson; Catherine R Culberson; Mark W Russo; Andrew S deLemos; Laura W Schrum Journal: Dig Dis Sci Date: 2018-01-12 Impact factor: 3.199
Authors: M Ujue Latasa; Carmen Gil-Puig; Maite G Fernández-Barrena; Carlos M Rodríguez-Ortigosa; Jesús M Banales; Raquel Urtasun; Saioa Goñi; Miriam Méndez; Sara Arcelus; Nerea Juanarena; Juan A Recio; Sophie Lotersztajn; Jesús Prieto; Carmen Berasain; Fernando J Corrales; Jon Lecanda; Matías A Avila Journal: PLoS One Date: 2010-12-29 Impact factor: 3.240
Authors: Rabea A Hall; Roman Liebe; Katrin Hochrath; Andrey Kazakov; Rudi Alberts; Ulrich Laufs; Michael Böhm; Hans-Peter Fischer; Robert W Williams; Klaus Schughart; Susanne N Weber; Frank Lammert Journal: PLoS One Date: 2014-02-28 Impact factor: 3.240