Involvement of fibroblast-specific protein 1 (S100A4) and matrix metalloproteinase-13 (MMP-13) in CCl4-induced reversible liver fibrosis

Introduction: The intense basic research on the molecular and cellular mechanisms of liver fibrosis regression intends to translate these findings into new therapies targeting such pathways in human liver disease. Fibrosis regression is rapidly initiated in mouse models of fibrosis within days after termination of the cause, so in this study, we investigated the expression of S100A4 and MMP-13 during liver fibrogenesis and remodeling. Methods: Thirty rats were divided into three groups: control group, fibrotic group, and fibrotic resolution group (10 each). The rats were sacrificed 48 h and 96 h after cessation of CCL-4, respectively. Liver tissue levels of S100A4 mRNA and S100A4 protein, MMP-13 mRNA and serum levels of serum TGF-beta 1, ALT and AST were determined. Results: Expression of S100A4 was increased during fibrotic stage and declined during resolution which was in correlation with the pro-fibrotic marker TGF-beta 1 with concordance about 90%, while MMP-13 expression increased in both stages reaching to 40 fold during resolution. Conclusion: These findings suggested that S100A4 level in the liver tissue was related positively with liver fibrosis making it a good marker for liver fibrogenesis and also a good target for novel antifibrotic strategies. (C) 2015 Elsevier B.V. All rights reserved.