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-beta1 (TGFbeta1). We treated carbon tetrachloride (CCl(4)) 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 (alphaSMA) indicated the less HSCs in CCl(4) treated rat liver with cholinergic denervation as compared to the sham-operated CCl(4) treated rats. It seems that cholinergic nerve not only innervates around the fibrosis area but also promotes HSCs. We also detected TGFbeta1 and BMP-6 expressions using RT-PCR and immunohistochemistry. The obtained results show that cholinergic denerveration decreases BMP-6 and TGF-beta1 expressions in CCl(4) induced liver fibrosis of rats. In conclusion, cholinergic nerve may influence HSCs in addition to the lowering of BMP-6 and TGF-beta1 gene expressions to modify liver fibrosis.
Lam
Hung-Bun
HB
Department of Surgery, Mackay Memorial Hospital, Taipei City 10401, Taiwan.
Yeh
Ching-Hua
CH
Cheng
Kai-Chun
KC
Hsu
Chao-Tien
CT
Cheng
Juei-Tang
JT
D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002799:Cholinergic Fibers / Q000502:physiology*; D003714:Denervation; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000294:innervation* / Q000378:metabolism; D008103:Liver Cirrhosis / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D010276:Parasympatholytics / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology
D000199:Actins; C525818:Bmp6 protein, rat; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins; D010276:Parasympatholytics; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D001285:Atropine; D002251:Carbon Tetrachloride; D000110:Acetylcholinesterase; D000109:Acetylcholine