title: Reduction of galectin-3 expression and liver fibrosis after cell therapy in a mouse model of cirrhosis.
abstract: OBJECTIVE
  Cirrhosis, end-stage liver disease, is caused by different mechanisms of injury, associated with persistent inflammation. Galectin-3 is an important regulator of fibrosis that links chronic inflammation to fibrogenesis. We investigated the role of bone marrow cell (BMC) transplantation in chronic inflammation and hepatic fibrosis.
  
  
  METHODS
  Liver cirrhosis was induced by administration of carbon tetrachloride and ethanol to wild-type C57BL/6 or bone marrow chimeric mice. Bone marrow chimeras were generated by lethal irradiation and transplantation with BMC obtained from green fluorescent protein (GFP(+) )donors. Wild-type cirrhotic mice were transplanted with BMC without irradiation. Livers from chimeras and cirrhotic transplanted mice were obtained for evaluation of inflammation, fibrosis and regulatory factors [galectin-3, matrix metallopeptidase (MMP)-9, tissue inhibitor of metalloproteinase (TIMP)-1 and transforming growth factor (TGF)-β].
  
  
  RESULTS
  The development of cirrhosis was associated with increased expression of galectin-3 by F4/80(+) cells and intense migration of BMC to the liver. Furthermore, when transplanted after the establishment of cirrhosis, BMC also migrated to the liver and localized within the fibrous septa. Two months after BMC therapy, cirrhotic mice had a significant reduction in liver fibrosis and expression of type I collagen. We did not find any difference in levels of TGF-β, TIMP-1 and MMP-9 between saline and BMC groups. However, the numbers of inflammatory cells, phagocytes and galectin-3(+) cells were markedly lower in the livers of cirrhotic mice treated with BMC.
  
  
  CONCLUSIONS
  Our results demonstrate an important role for BMC in the regulation of liver fibrosis and that transplantation of BMC can accelerate fibrosis regression through modulatory mechanisms.
authors.affiliation: Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, Pernambuco, Brazil.
authors.forename: Sheilla Andrade
authors.initials: SA
authors.lastname: de Oliveira
authors.forename: Bruno Solano
authors.initials: BS
authors.lastname: de Freitas Souza
authors.forename: Elton Pereira
authors.initials: EP
authors.lastname: Sá Barreto
authors.forename: Carla Martins
authors.initials: CM
authors.lastname: Kaneto
authors.forename: Hélio Almeida
authors.initials: HA
authors.lastname: Neto
authors.forename: Carine Machado
authors.initials: CM
authors.lastname: Azevedo
authors.forename: Elisalva Teixeira
authors.initials: ET
authors.lastname: Guimarães
authors.forename: Luiz Antonio Rodrigues
authors.initials: LA
authors.lastname: de Freitas
authors.forename: Ricardo
authors.initials: R
authors.lastname: Ribeiro-Dos-Santos
authors.forename: Milena Botelho Pereira
authors.initials: MB
authors.lastname: Soares
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000379:methods*; D002251:Carbon Tetrachloride / Q000008:administration & dosage / Q000009:adverse effects; D002465:Cell Movement; D002678:Chimera; D024042:Collagen Type I / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D037502:Galectin 3 / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007249:Inflammation; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000628:therapy*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010586:Phagocytes / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D018183:Transplantation Chimera
chemical_list: D024042:Collagen Type I; D037502:Galectin 3; C485095:Lgals3 protein, mouse; C560825:Timp1 protein, mouse; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D000431:Ethanol; D002251:Carbon Tetrachloride; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse