Systemic mediators induce fibrogenic effects in normal liver after partial bile duct ligation.
OBJECTIVE
Collagen production by activated hepatic stellate cells (HSCs) is a key event in liver fibrosis, and a number of factors have been characterized that trigger HSC activation and collagen production. However, it remains unclear if these factors act locally at the site of injury or also affect HSCs distant to the site of injury.


METHODS
A model of partial bile duct ligation (PBDL) in which fibrogenesis can be compared between the injured ligated lobe and the non-ligated lobe.


RESULTS
After PBDL, HSCs showed an increased expression of procollagen type I alpha1 mRNA and collagen-reporter gene activity not only in the ligated lobe, but also in the non-ligated lobe, albeit at a lower level. In contrast, an increase in the number of desmin- and alpha-smooth muscle actin positive HSCs, and accumulation of inflammatory cells were observed only in the ligated lobe. Although transforming growth factor-beta (TGF-beta) mRNA was increased only in the ligated lobe, Smad2/3 were activated in the ligated and the non-ligated lobe. These data suggest that the systemic increase in profibrogenic mediators including TGF-beta induces collagen transcription in the uninjured liver.


CONCLUSIONS
Systemic profibrogenic mediators from the injury site affect the residual non-injured liver.
Osawa
Yosuke
Y
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Seki
Ekihiro
E
Adachi
Masayuki
M
Taura
Kojiro
K
Kodama
Yuzo
Y
Siegmund
Soren V
SV
Schwabe
Robert F
RF
Brenner
David A
DA
D000199:Actins / Q000378:metabolism; D000818:Animals; D001652:Bile Ducts; D003094:Collagen / Q000235:genetics; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D003893:Desmin / Q000378:metabolism; D017930:Genes, Reporter; D007249:Inflammation / Q000209:etiology; D008026:Ligation; D008099:Liver / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D008103:Liver Cirrhosis / Q000209:etiology*; D051379:Mice; D008822:Mice, Transgenic; D009130:Muscle, Smooth / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000235:genetics; D015854:Up-Regulation
D000199:Actins; D024042:Collagen Type I; D003893:Desmin; D012333:RNA, Messenger; D051899:Smad2 Protein; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D003094:Collagen