Substance p-fibronectin-cytokine interactions in myeloproliferative disorders with bone marrow fibrosis.
Bone marrow (BM) fibrosis could occur secondarily to several clinical disorders: hematological and nonhematological. Clinical presentation of fibrosis could occur in myeloproliferative diseases, lymphoma, myelodysplastic syndrome and myeloma. The pathophysiology underlying BM fibrosis remains unclear despite intensive study, with a corresponding lack of specific therapy. This review discusses new insights in the role of substance P, cytokines and fibronectin in the development of BM fibrosis. Substance P is a neuropeptide that possesses pleiotropic properties, e.g. neurotransmission and immune/hematopoietic modulation and is linked to BM fibrosis. Cytokines and growth factors, in particular those associated with fibrogenic properties, e.g. TGF-beta, IL-1 and platelet-derived growth factor, are linked to BM fibrosis. Extracellular matrix proteins are increased in patients with BM fibrosis. Fibronectin in the sera of patients with BM fibrosis is complexed to substance P. Fibronectin appears to protect substance P from degradation by endogenous peptidases. This review describes the preliminary findings on the colocalization of substance P and fibronectin in the BM of patients with fibrosis. These data are reviewed in the context of published reports with particular focus on the relevant cytokines. A more detailed understanding of intra- and intercellular mechanisms in BM fibrosis may lead to effective therapy.
Rameshwar
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Department of Medicine, UMDNJ New Jersey Medical School, Newark, N.J. 07103, USA. rameshwa@umdnj.edu
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D016207:Cytokines / Q000378:metabolism*; D004347:Drug Interactions / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D009196:Myeloproliferative Disorders / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D055728:Primary Myelofibrosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D013373:Substance P / Q000378:metabolism*
D016207:Cytokines; D005353:Fibronectins; D013373:Substance P