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Bone marrow-derived fibrocytes participate in pathogenesis of liver fibrosis.
- 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.
- Subjects :
- Animals
Bone Marrow Cells metabolism
Cell Differentiation drug effects
Cell Differentiation genetics
Cells, Cultured
Collagen Type I genetics
Collagen Type I metabolism
Desmin genetics
Desmin metabolism
Fibroblasts metabolism
Green Fluorescent Proteins genetics
Green Fluorescent Proteins metabolism
Hepatocytes metabolism
Hepatocytes pathology
Leukocyte Common Antigens genetics
Leukocyte Common Antigens metabolism
Liver Cirrhosis metabolism
Mice
Mice, Inbred C57BL
Promoter Regions, Genetic genetics
Spleen metabolism
Spleen pathology
Transforming Growth Factor beta pharmacology
Bone Marrow Cells pathology
Fibroblasts pathology
Liver Cirrhosis etiology
Liver Cirrhosis pathology
Subjects
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