NOV/CCN3 is a matricellular protein of the CCN family, comprising CCN1 (CYR61), CCN2 (CTGF), CCN4 (WISP-1), CCN5 (WISP-2), and CCN6 (WISP-3). CCN proteins are involved in mitosis, adhesion, apoptosis, extracellular matrix production, growth arrest and migration of multiple cell types. Compared with CTGF, NOV has been studied to a lesser degree and its biological role in liver fibrosis remains primarily unknown. We therefore investigated hepatic expression of NOV in chronic liver injury upon long term CCl4 treatment and bile duct ligation (BDL) rat models. NOV gene expression was quantified by TaqMan RT-PCR, immunohistochemistry and ELISA. In both models of chronic liver injury, NOV mRNA showed significant and sustained upregulation. Specifically in BDL models, immunohistochemistry revealed clear expression of NOV protein in portal myofibroblasts, HSC and proliferative bile ducts along the fibrotic septa. Additionally, CCL4 models showed positive staining in particular regenerative hepatocytes. By contrast, TaqMan RT-PCR demonstrated no NOV expression in cultured hepatocytes isolated from naive and CCl4 treated rats. Culture-activated HSC however showed significant upregulation of NOV, reaching the highest levels in MFB.
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