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Bone marrow-derived fibrocytes participate in pathogenesis of liver fibrosis.

Abstract：

BACKGROUND/AIMS:Hepatic stellate cells (HSCs) play a key role in hepatic fibrogenesis. However, their origin is still unknown. We tested the hypothesis that bone marrow (BM) contributes to the population of HSCs. METHODS:Chimeric mice transplanted with donor BM from collagen alpha1(I)-GFP+ reporter mice were subjected to the bile duct ligation (BDL)-induced liver injury. RESULTS:In response to injury, BM-derived collagen-expressing GFP+ cells were detected in liver tissues of chimeric mice. However, these cells were not activated HSCs in that they did not express alpha-smooth muscle actin or desmin and could not be isolated with the HSC fraction. Meanwhile, the majority of these BM-derived cells co-expressed collagen-GFP+ and CD45+, suggesting that these cells represent a unique population of fibrocytes. Consistent with their lymphoid origin, the number of GFP+CD45+ fibrocytes found in BM and spleen of chimeric mice increased in response to injury. Fibrocytes cultured in the presence of TGF-beta1 differentiated into SMA+desmin+ collagen-producing myofibroblasts, potentially contributing to liver fibrosis. CONCLUSIONS:In response to the BDL-induced liver injury: (i) HSCs do not originate in the BM; (ii) collagen-producing fibrocytes are recruited from the BM to damaged liver.

journal_name

J Hepatol

journal_title

Journal of hepatology

authors

Kisseleva T,Uchinami H,Feirt N,Quintana-Bustamante O,Segovia JC,Schwabe RF,Brenner DA

doi

10.1016/j.jhep.2006.04.014

subject

Has Abstract

pub_date

2006-09-01 00:00:00

pages

429-38

issue

3

eissn

0168-8278

issn

1600-0641

pii

S0168-8278(06)00247-9

journal_volume

45

pub_type

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