Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.35 (matrix metalloproteinase 9)
 2,207 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using specific cDNAs isolated from mouse fibroblasts we determined tissue-specific expression of different matrix metalloproteinase genes: both stromelysin-1 and collagenase IV are highly expressed in heart and lung, whereas collagenase I is expressed most abundantly in skeletal muscle, kidney, and bone. High basal level expression of stromelysin-2 is found in heart and kidney. Like in man and rat, the expressions of collagenase I, stromelysin-1, and stromelysin-2 are regulated by the tumor promoter 12-O-tetradecanoyl-phorbol 13-acetate and by UV irradiation, but not by cAMP. In contrast, the expression of the 72-kDa collagenase IV is not affected by either stimuli. We and others have shown previously that under cell culture conditions, the regulation of human collagenase I is regulated by the transcription factor Fos/Jun (AP-1). Here we show that in c-fos transgenic mice transcription of collagenase I is induced in thymus, spleen, and, most dominantly, in bone upon overexpression of Fos. Neither collagenase IV nor stromelysin-1 or stromelysin-2 expression is affected by c-Fos. The sites of induced collagenase I expression correlate with the sites of Fos-induced long-term cellular alterations in transgenic mice including bone remodeling and T cell development. In fact, in the developing bone tumors strongly enhanced levels of collagenase I transcripts were detectable. These results identify collagenase I as a Fos-regulated gene in vivo and suggest a possible role for Fos/Jun heterodimers in establishing the pathological phenotype of c-fos transgenic mice.
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PMID:Phenotypic alterations in fos-transgenic mice correlate with changes in Fos/Jun-dependent collagenase type I expression. Regulation of mouse metalloproteinases by carcinogens, tumor promoters, cAMP, and Fos oncoprotein. 814 18

The family of matrix metalloproteinases (MMPs) is responsible for extracellular matrix degradation during physiological and pathophysiological tissue remodeling processes such as embryogenesis, tissue repair and cancer progression. Despite these important roles of MMPs, inhibition or ablation of individual members of the MMP family in animal models have been shown to have little effect. It has been speculated that this results from a functional overlap between individual MMPs and (as-yet-unclassified) functional overlaps between MMPs and other protease systems. We here present genetic data showing that concomitant ablation of MMP9 (gelatinase B) and the serine protease plasmin results in lethal inflammatory mass lesions in the colon. These lesions possessed several histological attributes that are characteristic of mucosal prolapse seen in humans, and they were found to be associated with splenomegaly, enlarged mesenteric lymph nodes, decreased thymus size and altered populations of circulating immune cells. A time-course study provided evidence that the massive lymphoid hyperplasia and reactive changes were secondary to discrete fibrinous lesions also observed in mice only deficient for plasminogen (Plg), the zymogen for plasmin. These data demonstrate a non-appreciated vital protective role for MMP9 in the absence of Plg.
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PMID:MMP9 is protective against lethal inflammatory mass lesions in the mouse colon. 2112 24