title: Bone marrow-derived fibrocytes contribute to liver fibrosis.
abstract: Chronic liver injury often leads to hepatic fibrosis, a condition associated with increased levels of circulating TGF-β1 and lipopolysaccharide, activation of myofibroblasts, and extensive deposition of extracellular matrix, mostly collagen Type I. Hepatic stellate cells are considered to be the major(1) but not the only source of myofibroblasts in the injured liver.(2) Hepatic myofibroblasts may also originate from portal fibroblasts, mesenchymal cells, and fibrocytes.(3) Since the discovery of fibrocytes in 1994 by Dr. Bucala and colleagues, this bone marrow (BM)-derived collagen Type I-producing CD45(+) cells remain the most fascinating cells of the hematopoietic system. Due to the ability to differentiate into collagen Type I producing cells/myofibroblasts, fibrocytes were implicated in the pathogenesis of liver, skin, lung, and kidney fibrosis. However, studies of different organs often contain controversial results on the number of fibrocytes recruited to the site of injury and their biological function. Furthermore, fibrocytes were implicated in the pathogenesis of sepsis and were shown to possess antimicrobial activity. Finally, in response to specific stimuli, fibrocytes can give rise to fully differentiated macrophages, suggesting that in concurrence with the high plasticity of hematopoietic cells, fibrocytes exhibit progenitor properties. Here, we summarize our current understanding of the role of CD45(+)Collagen Type I(+) BM-derived cells in response to fibrogenic liver injury and septicemia and discuss the most recent evidence supporting the critical role of fibrocytes in the mediation of pro-fibrogenic and/or pro-inflammatory responses.
authors.affiliation: Department of Medicine, University of California, San Diego, CA 92093, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Surgery, University of California, San Diego, CA 92093, USA tkisseleva@ucsd.edu.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Kisseleva
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D024042:Collagen Type I / Q000096:biosynthesis; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology; D018805:Sepsis / Q000378:metabolism* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human
keywords: Fibrocytes; bone marrow; collagen type I; liver fibrosis; myeloid cells; myofibroblasts