[go: up one dir, main page]

Migration of fibrocytes in fibrogenic liver injury

Am J Pathol. 2011 Jul;179(1):189-98. doi: 10.1016/j.ajpath.2011.03.049. Epub 2011 May 19.

Abstract

CD45(+) and collagen I-positive (Col(+)) fibrocytes are implicated in fibrogenesis in skin, lungs, and kidneys. Fibrocyte migration in response to liver injury was investigated using bone marrow (BM) from chimeric mice expressing luciferase (Col-Luc→wt) or green fluorescent protein (Col-GFP→wt) under control of the α1(I) collagen promoter and enhancer, respectively. Monitored by luciferase expression, recruitment of fibrocytes was detected in CCl(4)-damaged liver and in spleen. Migration of CD45(+)Col(+) fibrocytes was regulated by chemokine receptors CCR2 and CCR1, as demonstrated, respectively, by 50% and 25% inhibition of fibrocyte migration in Col-Luc(CCR2-/-)→wt and Col-Luc(CCR1-/-)→wt mice. In addition to CCR2 and CCR1, egress of BM CD45(+)Col(+) cells was regulated by transforming growth factor-β1 (TGF-β1) and liposaccharide in vitro and in vivo, which suggests that release of TGF-β1 and increased intestinal permeability have important roles in fibrocyte trafficking. In the injured liver, fibrocytes gave rise to (myo)fibroblasts. In addition, a BM population of CD45(+)Col(+) cells capable of differentiation into fibrocytes in culture was identified. Egress of CD45(+)Col(+) cells from BM was detected in the absence of injury or stress in aged mice but not in young mice. Development of liver fibrosis was also increased in aged mice and correlated with high numbers of liver fibrocytes. In conclusion, in response to liver injury, fibrocytes migrate from BM to the liver. Their migration is regulated by CCR2 and CCR1 but is compromised with age.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Blotting, Western
  • Bone Marrow / metabolism
  • Cell Adhesion
  • Cell Differentiation*
  • Cell Movement*
  • Cells, Cultured
  • Collagen / metabolism
  • Fibroblasts / cytology*
  • Fibroblasts / metabolism
  • Fluorescent Antibody Technique
  • Gene Expression Profiling
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Immunoenzyme Techniques
  • Leukocyte Common Antigens / genetics
  • Leukocyte Common Antigens / metabolism
  • Liver / injuries*
  • Liver / metabolism
  • Liver / pathology*
  • Liver Cirrhosis / pathology*
  • Luciferases / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myofibroblasts / cytology
  • Myofibroblasts / metabolism
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / genetics
  • Receptors, CCR1 / physiology
  • Receptors, CCR2 / physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spleen / injuries
  • Spleen / metabolism
  • Spleen / pathology
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Biomarkers
  • Ccr1 protein, mouse
  • Ccr2 protein, mouse
  • RNA, Messenger
  • Receptors, CCR1
  • Receptors, CCR2
  • Transforming Growth Factor beta1
  • Green Fluorescent Proteins
  • Collagen
  • Luciferases
  • Leukocyte Common Antigens
  • Ptprc protein, mouse