Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.17 (MMP-3)
 3,419 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exposure to the chemotherapeutic drug bleomycin leads to pulmonary fibrosis in humans and has been widely used in animal models of the disease. Using C57BL/6 bleomycin-sensitive mice, pulmonary fibrosis was induced by multiple intraperitoneal injections of the drug. An increase in the relative amounts of steady-state alpha1(I) procollagen, alpha1(III) procollagen, and fibronectin mRNA as well as histopathological evidence of fibrosis was observed. The effect of bleomycin on the expression of the enzymes responsible for extracellular matrix degradation, the matrix metalloproteinases (MMPs), and their inhibitors (TIMPs), was selective and showed temporal differences during the development of fibrosis. Of the MMPs tested, bleomycin treatment resulted in the up-regulation of gelatinase A and macrophage metalloelastase gene expression in whole-lung homogenates, whereas gelatinase B, stromelysin-1, and interstitial collagenase gene expression was not significantly changed. Timp2 and Timp3, the murine homologues of the respective TIMP genes, were constitutively expressed, whereas Timp1 was markedly up-regulated during fibrosis. The strong correlation between enhanced extracellular matrix gene expression, differential MMP and TIMP gene expression, and histopathological evidence of fibrosis suggest that dysregulated matrix remodeling is likely to contribute to the pathology of bleomycin-induced pulmonary fibrosis.
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PMID:Differential expression of extracellular matrix remodeling genes in a murine model of bleomycin-induced pulmonary fibrosis. 950 24

We investigated the mRNA and protein expression of fibronectin and stromelysin-1 (matrix metalloproteinase-3, MMP-3) by trabecular cells treated with growth factors present in primary and secondary aqueous humors. Serum-deprived trabecular cells were incubated for 48 hr or 7 days in medium containing either primary or secondary aqueous humor growth factors or in serum-free medium. We extracted total RNA, performed reverse transcription-polymerase chain reaction using primer pairs for fibronectin, stromelysin-1 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and quantified the products. We utilized Western blotting to detect and quantify fibronectin and stromelysin-1 protein. Compared to controls, expression of fibronectin mRNA by trabecular cells was increased by 50 and 100% after incubation in primary aqueous humor growth factors for 48 hr or 7 days, respectively, and 50 and 130% after incubation in secondary aqueous humor growth factors. Stromelysin-1 mRNA expression was decreased by 25 and 50% after incubation in primary aqueous humor growth factors for 48 hr or 7 days, respectively, and 80 and 85% after incubation for 48 hr or 7 days, respectively, in secondary aqueous humor growth factors. Fibronectin protein increased 3.5-fold and 6-fold after incubation for 48 hr with primary or secondary aqueous humor growth factors, respectively; after 7 days, the level increased 4- and 7-folds, respectively. Stromelysin-1 protein was not detectable by western blotting. The up-regulation of fibronectin mRNA by trabecular cells exposed to growth factors present in secondary aqueous humor augmented by the down-regulation of stromelysin-1 mRNA contributed to the accumulation of fibronectin. Our findings open the possibility that induction of stromelysin-1 gene expression in the trabecular meshwork of glaucomatous eyes could effectively reduce buildup of fibronectin in the aqueous outflow pathway to decrease outflow resistance in glaucomatous states of the eye.
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PMID:Trabecular cell expression of fibronectin and MMP-3 is modulated by aqueous humor growth factors. 1510 45