BACKGROUND AIMS: 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.
BACKGROUND AIMS: 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: Pierpaolo Pellicori; Concetta Torromeo; Angela Calicchia; Alessandra Ruffa; Martina Di Iorio; John G F Cleland; Manuela Merli Journal: Clin Res Cardiol Date: 2013-09-01 Impact factor: 5.460
Authors: Veruska Cintia Alexandrino de Souza; Danielle Maria Nascimento Moura; Maria Carolina Accioly Brelaz de Castro; Patrícia Torres Bozza; Ligia de Almeida Paiva; Camila Juliet Barbosa Fernandes; Renata Lins Carneiro Leão; Jéssica Paula Lucena; Roni Evencio de Araujo; Alex José de Melo Silva; Regina Celia Bressan Queiroz Figueiredo; Sheilla Andrade de Oliveira Journal: Sci Rep Date: 2019-04-23 Impact factor: 4.379
Authors: C M Kaneto; J S Nascimento; M C R Moreira; N D Ludovico; A P Santana; R A A Silva; I Silva-Jardim; J L Santos; S M B Sousa; P S P Lima Journal: Braz J Med Biol Res Date: 2017-10-19 Impact factor: 2.590