Cellular and molecular mechanisms underlying bone marrow and liver fibrosis: a review.
Chronic fibroproliferative diseases are an important cause of morbidity and mortality in the world. Fibrotic diseases occur in a large variety of vital organs, and the process of fibrosis seems common to all tissues. In all of fibrotic reactions, the underlying cellular and molecular mechanisms involve leukocyte infiltration, the persistence of inflammation in the tissue, and the proliferation of cells with a myofibroblast phenotype. The different cell types participating to this process sustain production of growth factors, proteolytic enzymes, angiogenic factors, and fibrogenic cytokines, which together stimulate the deposition of connective tissue elements that progressively destroy and remodel normal tissue architecture. This review focuses on the comparison of two, major, chronic fibroproliferative diseases: the myelofibrosis which develops in bone marrow, a "fluid" tissue producing circulating haematopoietic cells, and liver fibrosis, which demonstrates all the features of solid tissue damage. We discuss the etiology and histological quantification of each type of fibrosis, the implication of cell partners, cytokines and growth factors, animal models developed to study fibrosis, and antifibrotic therapies for each of these two fibroproliferative disease models.
Le Bousse-Kerdilès
Marie-Caroline
MC
INSERM U602, Hôpital Paul-Brousse, 14 Avenue Paul-Vaillant Couturier, 94807 Villejuif Cedex, France.
Martyré
Marie-Claire
MC
Samson
Michel
M
D000818:Animals; D001853:Bone Marrow / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008103:Liver Cirrhosis / Q000150:complications / Q000473:pathology* / Q000628:therapy; D051379:Mice; D008954:Models, Biological; D055728:Primary Myelofibrosis / Q000150:complications / Q000175:diagnosis; D016212:Transforming Growth Factor beta / Q000378:metabolism
D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D016212:Transforming Growth Factor beta