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

The effect of colchicine and vinblastine on collagenase, lysyl oxidase and prolyl hydroxylase activities as well as on collagen cross-linking and types of this protein in bleomycin induced lung fibrosis in rats was investigated. Both colchicine and vinblastine diminish bleomycin-induced changes in the above-mentioned enzyme activities as well as collagen cross-linking and normalize type I/type III collagen ratio.
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PMID:The effect of colchicine and vinblastine on bleomycin-induced lung fibrosis in rats. 754 Mar 48

Antibodies were raised against seven major matrix metalloproteinases: stromelysin-1 (MMP-3), stromelysin-2 (MMP-10), stromelysin-3 (MMP-11), interstitial collagenase (MMP-1), M(r) 72,000 type IV collagenase (72 kDa type IV collagenase, MMP-2), M(r) 92,000 type IV collagenase (92 kDa type IV collagenase, MMP-9) and matrilysin (PUMP, MMP-7) as well as against prolyl 4-hydroxylase, to study the expression of these collagenolytic enzymes in normal liver in relation to the activity of collagen synthesis. Tissue samples of four normal human livers, three hepatocellular carcinomas and one cholangiocellular carcinoma were analysed. In normal liver we found expression of stromelysin-1, stromelysin-3, interstitial collagenase, M(r) 72,000 and M(r) 92,000 type IV collagenases and varying expression of prolyl 4-hydroxylase. Stromelysin-2 was inconsistently detectable; matrilysin was not found. In hepatocellular carcinoma the expression pattern of matrix metalloproteinases showed only minor changes compared with the normal tissue; stronger signals than in normal tissue were seen for stromelysin-1, and stromelysin-2 was also strongly positive. M(r) 72,000 and M(r) 92,000 type IV collagenases and interstitial collagenase were less strongly expressed; stromelysin-3 was unchanged. Expression of prolyl 4-hydroxylase was also increased compared with normal liver. Matrilysin was only seen in cholangiocellular carcinoma, which showed a completely different pattern of matrix metalloproteinase expression. Our results show that metalloproteinases are expressed in human liver with much greater abundance than previously described. Their expression pattern is not changed fundamentally in hepatocellular carcinoma but is completely different from that of other tumour tissues such as cholangiocellular carcinoma.
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PMID:Expression pattern of matrix metalloproteinases in human liver. 763 22

Collagen synthesis and degradation in normal and carbon-tetrachloride-injured male Wistar rats at early and late stages of liver fibrosis, and the potential beneficial effects of zinc supplementation on liver fibrogenesis and collagenolysis have been assessed by measuring hepatic collagen content and prolyl hydroxylase and collagenase activities. No significant changes in hepatic collagen and prolyl hydroxylase activities were observed between control rats (82 +/- 25 cpm/mg protein) and rats with induced cirrhosis (107 +/- 23 cpm/mg protein) after 4 weeks of carbon tetrachloride injury. By this time, hepatic collagenase activity was significantly lower in rats with induced cirrhosis (61 +/- 9 micro units/mg protein) than in control rats (133 +/- 31 micro units/mg protein) (p < 0.05). This result was prevented by zinc administration, since hepatic collagenase activity was similar in zinc-supplemented, carbon-tetrachloride-injured rats and normal rats (148 +/- 19 micromicrons/mg protein). After 16 weeks, all carbon-tetrachloride-injured rats had cirrhosis. Hepatic collagen content and prolyl hydroxylase activity were significantly higher in carbon-tetrachloride-injured rats than in controls. These effects were partially prevented by zinc administration, since only two of the seven zinc-supplemented, carbon-tetrachloride-injured rats had cirrhosis. Moreover, prolyl hydroxylase activity was significantly lower in zinc-supplemented injured rats (263 +/- 27 cpm/mg protein) than in the non-supplemented respective controls (389 +/- 52 cpm/mg protein) (p < 0.05). No significant changes in hepatic collagenase activity were observed at this stage of liver injury.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fibrogenic and collagenolytic activity in carbon-tetrachloride-injured rats: beneficial effects of zinc administration. 783 96

Contribution of collagen to cell proliferation was studied in cultured hepatocytes. When alpha,alpha'-dipyridyl, an iron chelator which blocks hydroxylation of prolyl and lysyl residues of procollagen and expression of procollagen mRNA, was added to the medium of rat hepatocytes in primary culture, DNA synthesis of the cells was reduced in a dose-related manner without changes in protein synthesis. The reduction of collagen synthesis was parallel with the changes of DNA synthesis. The addition of P-1894B or minoxidil, which inhibits specifically prolyl hydroxylase or lysyl hydroxylase, respectively, also produced similar results. However, the DNA synthesis was not affected by beta-aminopropionitrile fumarate, which inhibits cross linking in extracellular collagen maturation, nor by purified bacterial collagenase. Intracellular processing of collagen synthesis may be required for proliferation in cultured rat hepatocytes.
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PMID:Evidence that impaired intracellular collagen synthesis reduces proliferation in cultured rat hepatocytes. 818 28

The present study was conducted to isolate and to characterize stromal cells from the human prostate and to study the effects of androgen and different growth factors in this model system. Benign prostatic hyperplasia (BPH) tissue samples were obtained from transurethral resection of the prostate (TURP). Tissue specimens were mechanically and enzymatically dissociated by treatment with DNAse and collagenase. Epithelial cells were separated from stromal cells by discontinuous Percoll gradient centrifugation. The stromal cells obtained were cultured in phenol red-free RPMI-1640 supplemented with 10% fetal bovine serum. Immunocytochemical analysis revealed that the stromal cell cultures were composed of both smooth muscle cells and fibroblasts. The short and broad, smooth muscle cells wee identified by using an antibody directed against alpha-smooth muscle actin. The thin and elongated fibroblasts stained positively for prolyl 4-hydroxylase. Smooth muscle cells were the predominant cell type in the present investigation. Typical cultures contained up to 99% of cells staining positively for alpha-smooth muscle actin. The prostate smooth muscle cultures were treated with dihydrotestosterone (DHT), bovine pituitary extract (BPE), basic fibroblast growth factor (bFGF) and transforming growth factor-beta (TGF-beta). When cells were cultured in serum free RPMI-1640 supplemented with ITS+ (insulin, transferrin, and selenious acid) no significant (P > 0.05) mitogenic effect in medium supplemented with ITS+. In the presence of 10% charcoal-stripped fetal bovine serum (cFBS) DHT, at a concentration of 0.1 nM, was able to cause a slight but significant (P < 0.05) mitogenic effect on BPH smooth muscle cells growth. Basic FGF was able to stimulate BPH smooth muscle cells in a concentration-dependent fashion. The combination of DHT and 0.1 ng/ml bFGF was able to increase the proliferation of prostate smooth muscle cells above either agents alone. Addition of BPE to serum free RPMI-1640 caused a significant (P < 0.05) stimulation of cell proliferation in a concentration-dependent fashion. Addition to TGF-beta to serum or BPE containing RPMI-1640 caused a significant (P < 0.05) inhibition to cell proliferation in a concentration-dependent fashion. TGF-beta was cytostatic to the benign prostatic smooth muscle cells only in the presence of media containing growth stimulating factors found in charcoal-stripped serum or in bovine pituitary extract. These results demonstrated that stromal fraction isolated from BPH specimens was composed of both fibroblasts and smooth muscle cells. These cells could be cultured and were able to respond to various growth stimulatory and inhibitory agents.
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PMID:Stromal cells of the human prostate: initial isolation and characterization. 860 97

In order to elucidate collagen metabolism in hepatocellular carcinoma (HCC) tissue, we compared levels of different potential markers of collagen metabolism and plasma transforming growth factor-beta 1 in patients with HCC and in patients with liver cirrhosis. Serum levels of prolyl hydroxylase and the tissue inhibitor of metalloproteinase-1 in patients with HCC were significantly higher than those in patients with liver cirrhosis and increased with the size of the HCC tumour, whereas the serum levels of procollagen type III propeptide and type IV collagen 7S domain were similar in the two groups. In HCC, the increased plasma transforming growth factor-beta 1 levels were closely correlated with serum levels of prolyl hydroxylase and the tissue inhibitor of metalloproteinase-1. These findings suggest that, in HCC tissue, the intracellular biosynthesis of collagen is enhanced, whereas the secretion of procollagen is disturbed and the degradation of collagen is suppressed by the excess production of the tissue inhibitor of metalloproteinase-1. The results also suggest that plasma transforming growth factor-beta 1 plays an important role in the altered metabolism of collagen in HCC.
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PMID:Serum markers for fibrosis and plasma transforming growth factor-beta 1 in patients with hepatocellular carcinoma in comparison with patients with liver cirrhosis. 874 16

Cultures were established from adherent cells of synovial fluid and from collagenase-dispersed specimens of synovial tissue. In cultures derived from synovial tissue, prolyl hydroxylase-positive cells of fibroblast-like morphology were identified as the predominant cell type. In cultures from synovial fluid the majority of adherent cells was macrophage-like in appearance and strongly positive for CD 68. Cells with a stellate morphology could rarely be observed in cultures from synovial tissue. Their relations to other forms will be discussed. Several simple methods for cultivating adherent synovial cells are presented.
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PMID:Primary cultivation of human synovial cells from nonrheumatic synovial tissue and fluid. 881 Dec 90

The pathogenesis of chronic pancreatitis (CP) has been debated as to whether it is a de novo process or the consequence of acute pancreatitis (AP). We investigated whether recurrent AP in rats leads to CP, by sequential morphological and biochemical studies. Thirty male Wistar rats were fed a choline-deficient diet with intraperitoneal ethionine injections twice daily at a dose of 60 mg/100 g body weight twice weekly, and six rats were killed at 4, 6, and 8 weeks; the remaining 12 rats, followed without further treatment, were killed at 12 and 16 weeks. The pancreata from study and control groups were examined by histology, immunohistochemistry, and bio- and immunoassays. Histologically, moderate to severe intra- and perilobular fibrosis and other CP-like lesions appeared maximally at 8 weeks. Immunohistochemically, the earliest extracellular matrix change was strong fibronectin staining at 4 weeks, with a progressive increase to 8 weeks. Collagens I and III came to show strong, and collagen IV moderate, interstitial staining at 6-8 weeks. These morphological changes, however, returned to nearly normal at 16 weeks. Prolyl hydroxylase was significantly elevated at 4 and 6 weeks and normalized after 8 weeks, with no significant change in collagenase. In conclusion, our results suggest that even severe CP-like lesions induced by recurrent AP are reversible in the absence of persistently elevated prolyl hydroxylase and/or suppressed collagenase. The mechanism regulating these changes remains to be studied further.
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PMID:Does recurrent acute pancreatitis lead to chronic pancreatitis? Sequential morphological and biochemical studies. 916 78

We investigated the time-course of changes in pancreatic fibrosis accompanied with pancreatitis in WBN/Kob rats. The areas of fibrosis and fatty replacement were analysed morphometrically, and biochemical measurements of pancreatic and plasma prolyl hydroxylase and of pancreatic collagenase were assessed. Male rats showed acute pancreatitis at 2-3 months of age, lesions that later underwent a transition to widespread fibrosis. The fibrosis then decreased, and the fibrotic tissue was replaced with adipose tissue. Morphometrically, the fibrotic area reached its maximal size when the rats were 4 months old, diminishing thereafter. The fibrosis occurred mainly in the intralobular space, and was principally attributable to type-III collagen. Type-I collagen scarcely appeared throughout the experimental period. Alpha-Smooth muscle actin appeared in and around myofibroblasts that developed in an early stage and diminished later in accordance with the progressive manner of fibrosis. The plasma prolyl hydroxylase level was higher in males than in females from 4 through 10 months of age. Pancreatic collagenase activity in the males also increased during the same period. These findings suggest that pancreatic fibrosis in male WBN/Kob rats is affected by the balance between prolyl hydroxylase and collagenase.
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PMID:Histopathological and biochemical studies on pancreatic fibrosis in WBN/Kob rats. 1007 Dec 40

The effects of a prolyl 4-hydroxylase inhibitor (HOE 077) on tissue inhibitor of metalloproteinase-1 (TIMP-1) and procollagen type I were examined in rat liver fibrosis. HOE 077 (200 ppm) prevented fibrosis by inhibiting the expression of liver type I procollagen and TIMP-1 mRNAs, with liver hydroxyroline content correlated with the reduction in activated stellate cells. HOE 077 prevents fibrosis by inhibiting proline hydroxylation and stellate cell activation, resulting in reduced expression of procollagen and TIMP-1 mRNAs.
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PMID:Prolyl 4-hydroxylase inhibitor (HOE 077) prevents TIMP-1 gene expression in rat liver fibrosis. 1043 15


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