Effect of cholinergic denervation on hepatic fibrosis induced by carbon tetrachloride in rats

Various factors involved in the development of liver fibrosis, including hepatic stellate cells (HSCs), cholinergic nervous activity and fibrogenetic cytokines. The present study aims to investigate the role of cholinergic regulation in the promoting of liver fibrogenesis relating to bone morphogenetic protein-6 (BMP-6) and/or transforming growth factor-beta 1 (TGF beta 1). We treated carbon tetrachloride (CCl4) into rats for eight weeks to induce liver fibrosis and arranged these rats for cholinergic denervation, hepatic branch vagotomy or atropine administration. Acetylcholinesterase (AChE) staining showed the distribution of cholinergic nerve around fibrosis scaring septa. The immunohistochemical staining for alpha smooth muscle actin (alpha SMA) indicated the less HSCs in CCl4 treated rat liver with cholinergic denervation as compared to the sham-operated CCl4 treated rats. It seems that cholinergic nerve not only innervates around the fibrosis area but also promotes HSCs. We also detected TGF beta 1 and BMP-6 expressions using RT-PCR and immunohistochemistry. The obtained results show that cholinergic denerveration decreases BMP-6 and TGF-beta 1 expressions in CCl4 induced liver fibrosis of rats. In conclusion, cholinergic nerve may influence HSCs in addition to the lowering of BMP-6 and TGF-beta 1 gene expressions to modify liver fibrosis. (C) 2008 Elsevier Ireland Ltd. All rights reserved.