Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1,25 Dihydroxyvitamin D3 is a differentiation inducer for monocytic cell. It can induce a monoblastic cell line U937 to differentiate. In this paper, we report that by inducing the differentiation of U937, 1,25-dihydroxyvitamin D3 increased urokinase activity expression on U937 cell surfaces. After incubation of the cell with various concentrations of 1,25-dihydroxyvitamin D3, the cell line showed a remarkable progressively increasing membrane-associated urokinase activity in a dose dependent manner. On the contrary, plasminogen activator inhibitor activity which was found in the culture medium is not modified by the 1,25-dihydroxyvitamin D3 induction. This results suggests another role of 1,25-hydroxyvitamin D3 in the treatment of myelofibrosis, since enhanced plasmin generation can accelerate the activation of procollagenase. The induced plasmin and collagenase activities surrounding the monocytic cells may participate in the physiological and pathological events, especially in the connective tissue degradation.
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PMID:Enhanced expression of urokinase activity on U 937 cell line by 1,25-dihydroxyvitamin D3 induction. 314 69

It is proposed that interferon may be an active agent in the treatment of patients with idiopathic myelofibrosis. In this disorder the megakaryocyte cell lineage plays a major role in the deposition of bone marrow collagen by the release of growth promoting factors, including platelet-derived growth factor, which are mitogenic for fibroblast proliferation. Interferon reduces collagen deposition in the bone marrow by suppressing the activity of the proto-oncogene, which is involved in the production of growth factors from abnormal megakaryocytes and platelets. A direct myeloid cytoreductive effect of interferon upon the megakaryocyte proliferation contributes to reducing growth factor activity in the bone marrow. Finally, interferon induces monocytoid differentiation, thereby increasing bone marrow collagenase-activity. Thus, interferon has several actions, which in concert might reduce bone marrow collagen in myelofibrosis.
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PMID:Hypothesis: a possible role for interferon in the treatment of idiopathic myelofibrosis. 322 65

In this article current concepts on the regulation of bone marrow collagen are reviewed and a hypothesis regarding the mechanisms leading to marrow fibrosis associated with Primary Myelofibrosis (PMF) is presented. Type I and type III collagen, products of marrow fibroblasts, are the main constituents of myelofibrotic tissue and megakaryocytes are the predominant cells proliferating in PMF. There is evidence for the clonal nature of the hematopoietic cell proliferation and the secondary origin of myelofibrosis. Also, evidence exists indicating that defective megakaryocyte maturation, i.e. ineffective megakaryocytopoiesis occurs in patients with PMF. It is postulated that ineffective megakaryocytopoiesis leads to an excessive concentration of megakaryocyte components in the marrow intercellular space and that the development of marrow fibrosis involves mainly 2 megakaryocytic products: growth factor and factor 4. The growth factor stimulates fibroblast proliferation and collagen secretion. Factor 4 inhibits the activity of the enzyme collagenase. Thus, the imbalance between increased collagen production and decreased collagen degradation leads to an excessive deposition of collagens in bone marrow matrix.
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PMID:Pathophysiological mechanisms operating in the development of myelofibrosis: role of megakaryocytes. 629 27

Chronic myelogenous leukaemia (CML) is frequently accompanied by progressive myelofibrosis that is probably largely due to increased collagen production by bone marrow fibroblasts or decreased collagen degradation by collagenase. We investigated the activity of collagenase and collagenase-inhibitory factors (CIF) in serum and bone marrow fibroblast-conditioned medium obtained from patients with CML and healthy volunteers. The activity of both collagenase and CIF was significantly higher in the CML patients than in the normal volunteers. Our previous study showed that bone marrow fibroblasts from CML patients produce significantly more collagen than fibroblasts from normal subjects. Therefore, it appears that the in vitro production of collagenase and CIF by bone marrow fibroblasts is related to the degree of in vivo collagen production. and that both the increased collagenase and CIF activities are reflections of collagen overproduction in CML.
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PMID:Collagenase activity and collagenase-inhibitory factors of serum and bone marrow fibroblast-conditioned medium in chronic myelogenous leukaemia. 751 66

Bone marrow fibrosis in chronic idiopathic myelofibrosis (cIMF) most likely represents an imbalance between synthesis and turnover of collagen fibers. Because the JAK-STAT signaling pathway is involved in the regulation of genes encoding matrix metalloproteinases (MMPs), we examined the expression of MMPs, their tissue inhibitors (TIMPs), and collagen types in relation to the JAK2 status (V617F mutation versus wild-type) in cIMF (n = 64). Whereas no correlation was found between the JAK2 status and MMP gene products, there was an evident association with the stage of disease. Membrane type 1-MMP (MMP-14) was overexpressed by up to 80-fold in advanced stages that progressed to fibrosis (P < 0.001), and megakaryocytes and endothelial cells were unmasked as the major cellular source. By contrast, a significantly higher expression of neutrophil collagenase (MMP-8) was encountered in the prefibrotic stages of cIMF (P < 0.001). Altogether, the stepwise progress of myelofibrosis in cIMF was associated with expression of a defined subset of target genes as shown in sequential trephine biopsies of cIMF patients. We conclude that the expression of matrix-modeling genes in cIMF is not influenced by the JAK2 mutation status but is predominantly related to the stage of disease.
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PMID:Aberrant collagenase expression in chronic idiopathic myelofibrosis is related to the stage of disease but not to the JAK2 mutation status. 1687 49