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

Authors :
Kisseleva T
Uchinami H
Feirt N
Quintana-Bustamante O
Segovia JC
Schwabe RF
Brenner DA
Source :
Journal of hepatology [J Hepatol] 2006 Sep; Vol. 45 (3), pp. 429-38. Date of Electronic Publication: 2006 Jun 09.
Publication Year :
2006

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.<br />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.<br />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.<br />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.

Details

Language :
English
ISSN :
0168-8278
Volume :
45
Issue :
3
Database :
MEDLINE
Journal :
Journal of hepatology
Publication Type :
Academic Journal
Accession number :
16846660
Full Text :
https://doi.org/10.1016/j.jhep.2006.04.014