Participation of bone marrow cells in biliary fibrosis after bile duct ligation.
OBJECTIVE
Bone marrow derived cells are involved in the process of hepatic fibrosis secondary to chronic injury. However, it is not yet known how quickly this event occurs in acute fibrosis models. The purpose of this study was to determine the role of bone marrow cells in rapid fibrosis following bile duct ligation in mice using green fluorescent protein (GFP) expressing bone marrow cells.


METHODS
After whole body irradiation, 1 x 10(6) donor whole bone marrow cells from green fluorescent protein(+/-) mice were transplanted into C57BL/6 recipients via the tail vein. Four weeks after bone marrow transplantation, chimeric mice were subjected to common bile duct ligation, and livers of these animals were histologically examined after bile duct ligation using anti-fibroblast specific protein (FSP)-1 antibody and anti-alpha-smooth muscle actin (alpha-SMA) antibody.


RESULTS
Periductal fibrosis consisting of fibroblast specific protein-positive cells was demonstrated histologically as early as day 7. Most of the fibrotic cells were green fluorescent protein-negative, however, a significant number of cells were green fluorescent protein-positive and some were also anti-FSP or alpha-SMA-positive.


CONCLUSIONS
Differentiation of bone marrow derived cells into activated fibroblast and myofibroblast-like phenotypes occurs in the very early course of periductal fibrosis following bile duct ligation, suggesting a new strategy for prevention of biliary fibrosis by inhibiting migration of bone marrow cells to liver.
Asawa
Sadanori
S
First Department of Surgery, Fukushima Medical University, Fukushima, Japan.
Saito
Takuro
T
Satoh
Atai
A
Ohtake
Koich
K
Tsuchiya
Takao
T
Okada
Hirokazu
H
Neilson
Erik G
EG
Gotoh
Mitsukazu
M
D000199:Actins / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement; D002678:Chimera; D003135:Common Bile Duct / Q000601:surgery*; D003137:Common Bile Duct Diseases / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008026:Ligation; D008103:Liver Cirrhosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008111:Liver Function Tests; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; D013997:Time Factors; D014916:Whole-Body Irradiation
D000199:Actins; D002135:Calcium-Binding Proteins; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C470944:S100a4 protein, mouse; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins