Fig. 12
From: Fibrosis and bone marrow: understanding causation and pathobiology
Molecular pathways leading to fibrosis of tissue including bone marrow. TGF beta is the most important growth factor causing fibrosis in the marrow. This growth factor is released by a subset of megakaryocytes and mesenchymal stem cells as well as macrophages and activated lymphocytes and metastatic malignant cells. Release in the marrow stroma is assisted by integrin ligands. Growth factors like fibroblast growth factor, cytokines and vasoactive peptides activate their cognate receptors and via MAP kinase, Rho kinase and other intracellular kinases induce gene transcription for synthesis of collagen. Some of these factors also activate either MMPs or its inhibitor TIMP