Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

PTH administration in vivo increases osteoblast number and activity, resulting in increased bone formation, and also increases osteoclast-mediated bone resorption. Studies in vitro, however, have shown that the actions of PTH on osteoblast-like cells are inhibitory and catabolic, as shown by decreases in growth rate and collagen synthesis and increases in collagenase production. The present studies were designed to investigate possible mechanisms for these observations by examining the effects of PTH on the response of osteoblast-like cells to the osteoblast growth factor, epidermal growth factor (EGF). Confluent cultures of UMR 106-01 cells were treated with rat PTH-(1-34) for periods up to 72 h, and EGF receptors were measured with [125I]EGF. PTH, in a dose- and time-dependent manner, increased the number of EGF receptors 2-fold. The half-maximal effect of PTH occurred at a concentration of 1 nM, the same PTH concentration that resulted in half-maximal increases in cAMP generation. The increase in EGF binding was associated with an enhanced biological effect, as shown by augmentation of EGF-stimulated diglyceride production. The effect of PTH could be reproduced by the addition of 8-bromo-cAMP, but not by the phorbol ester phorbol myristate acetate. In the presence of cyclohexamide, the effect of PTH on EGF binding was abolished, suggesting that new protein synthesis was required to increase the number of EGF receptors. Northern blots of total RNA, using a cDNA probe encoding the extracellular domain of the rat EGF receptor, revealed that PTH treatment resulted in a 2- to 3-fold increase in the level of EGF receptor mRNA. These data suggest that the proliferative effects of PTH on the osteoblast may be mediated indirectly by a PTH-induced increase in the number of EGF receptors.
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PMID:Parathyroid hormone increases the expression of receptors for epidermal growth factor in UMR 106-01 cells. 813 37

The effects of transforming growth factor-beta (TGF beta) and epidermal growth factor (EGF) on the synthesis of collagen and fibronectin, and on the proliferation of human corneal stromal fibroblasts in vitro, were evaluated. Human corneal stromal fibroblasts in culture were incubated for 48 hours with TGF beta or EGF in the absence of serum. Collagen and fibronectin in the culture media were measured by a collagenase-digestion assay and a competitive ELISA, respectively. The effects of the growth factors on proliferation were assessed by 3H-thymidine incorporation. Collagen synthesis was dose-dependently stimulated by TGF beta; at a concentration of 1 ng/ml of TGF beta, a 120% increase in collagen synthesis was seen over that of controls (p < 0.01). EGF, at a concentration of 10 ng/ml, induced a 40% increase in collagen synthesis over that of controls (p < 0.01). The maximum stimulation by TGF beta was greater than that by EGF (p < 0.05). Fibronectin synthesis was stimulated by TGF beta and EGF in a dose-dependent manner; 230% (p < 0.001) and 210% (p < 0.01) increases in fibronectin synthesis were caused by 10 ng/ml TGF beta and EGF, respectively. TGF beta and EGF dose-dependently stimulated 3H-thymidine incorporation. The maximum increases in 3H-thymidine incorporation reached 180% (p < 0.001) and 190% (p < 0.001) over that in controls, at 10 ng/ml concentrations of TGF beta and EGF, respectively. In conclusion, both TGF beta and EGF are potent stimulants of collagen and fibronectin synthesis and proliferation. Therefore, these two growth factors may be effective alternatives or additional choices for the treatment of corneal ulcer.
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PMID:Transforming growth factor-beta stimulates collagen and fibronectin synthesis by human corneal stromal fibroblasts in vitro. 822 30

The effects of recombinant human interleukin-1 alpha (IL-1 alpha) and murine epidermal growth factor (EGF) on the release of collagenase were studied in an in vitro model system using periosteal explants from rabbit calvariae. Following an incubation period of 72 h it was shown that IL-1 alpha in combination with EGF (IL-1 alpha + EGF) induced a synergistic increase in the amount of collagenase released by periosteal explants. This increase appeared to be at least 10-fold. Most of the enzyme was present in a latent form since the increase in enzyme activity was only detectable after activation by APMA and the molecular weight as determined in immunoblots corresponded to the latent form of this enzyme. Incubations carried out with IL-1 alpha alone resulted in a 2- to 4-fold increase of total enzyme activity, whereas the amount of collagenase in media of EGF-treated periosteal did not surpass control values. A neutralizing anti-IL-1 alpha antibody completely blocked the enhanced release of collagenase as induced both by IL-1 alpha and by IL-1 alpha + EGF. Indomethacin partially prevented the IL-1 alpha + EGF-induced increase in enzyme release, suggesting the involvement of prostaglandins. The amount of tissue inhibitor of metalloproteinases (TIMP) as determined by ELISA was slightly elevated in culture media obtained from all cytokine-treated explants. Comparable results were obtained by Western blot analysis as well as by a functional bioassay. It is suggested that the concomitant presence of the cytokines IL-1 alpha and EGF may play an important role in collagenase-mediated degradation of collagen.
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PMID:Interleukin-1 alpha and epidermal growth factor synergistically enhance the release of collagenase by periosteal connective tissue in vitro. 824 34

During embryonic development presumptive hair follicle cells of epithelial and mesenchymal origin are determined in defined body locations. This is followed by rapid proliferation of epithelial cells and associated penetration into the dermis in response to as yet undetermined signals. A collagen matrix culture system, which maintains the three-dimensional relationships of hair follicle cells to each other, was developed to study the regulation of the enlargement of immature hair follicles and the accompanying remodeling of the dermis. In studies with a heterogeneous dermis-derived preparation of murine hair follicles, ranging in size from the earliest down-growing budding cell mass to hair-forming follicles, we had previously shown that cell proliferation was stimulated by cholera toxin and epidermal growth factor, but only the epidermal growth factor-stimulated proliferation was accompanied by digestion of the collagen matrix due to release of collagenolytic enzymes. Further studies revealed that transforming growth factor-alpha also stimulated hair follicle cell proliferation and collagenase release. However, although transforming growth factor-beta inhibited the transforming growth factor-alpha-stimulated proliferation, it enhanced the release and activation of collagenases and other gelatin-degrading enzymes detectable by gelatin zymography. Stimulation of collagenolytic activity depended on the three-dimensional hair follicle structure and did not occur in monolayer cultures of hair follicle cells. Comparison of hair follicle buds with more developed dermis-derived hair follicles, plated at the same cell density (based on DNA content), suggested that a greater fraction of cells in the bud-stage follicle responded to the growth factors by release of collagenases. Possibly only the cells in the advancing portion of growing hair follicles that are closest to the dermal papilla cell cluster produce the collagenases in response to growth factors. To examine the participation of dermal papilla cells in collagenase release and activation, several immortalized rat whisker dermal papilla cell lines were co-cultured with mouse hair follicle buds. Co-culture resulted in a marked enlargement of follicles as well as activation of the 92-kDa type IV collagenase, produced by hair follicle buds, that correlated with ability of the dermal papilla cells to stimulate hair formation in grafts of hair follicle buds on nude mice. Dermal papilla cells cultured alone produced the 72-kDa type IV collagenase, which was also activated during co-culture with hair follicle buds. Thus, two activities, both relevant for hair follicle development, namely, cell proliferation and release and activation of collagenases, have been stimulated in immature hair follicle buds by either growth-factor supplementation or interaction with dermal papilla cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Regulation of hair follicle development: an in vitro model for hair follicle invasion of dermis and associated connective tissue remodeling. 832 51

Hepatocytes maintained in collagen gels remain differentiated for prolonged periods of time compared to cells maintained on conventional cultures. Previous studies with other culture systems in which chemical supplements or substratum modifications enhanced hepatocyte differentiation showed that in all of these systems hepatocytes do not respond to mitogens. In this study it is shown that hepatocytes maintained between two layers of collagen gels respond to mitogens HGF (also known as scatter factor (HGF/SF)) and epidermal growth factor (EGF). Cell density did not affect the responsiveness to mitogens as in conventional cultures. In addition both mitogens (HGF more pronounced) induce characteristic morphogenic changes in which hepatocytes form processes and join in formation of cords. Hepatocytes respond to mitogens for up to 6 days in culture at which point they become refractory to further mitogenic stimulation. This occurs despite electron microscopic evidence that these cells are fully viable when they become refractory to mitogenesis. The refractory state is not modified by substitution of one growth factor for the other or by addition of growth factors at different times. Hepatocytes in the refractory state become again responsive to mitogens when the collagen gels are dispersed by collagenase and the cells are replated on conventional substrates.
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PMID:Comparative analysis of mitogenic and morphogenic effects of HGF and EGF on rat and human hepatocytes maintained in collagen gels. 836 Feb 54

Rat mucosal keratinocytes serially propagated under permanently serum-free conditions responded to interleukin (IL)-1 beta/IL-alpha and to transforming growth factor (TGF)-alpha/epidermal growth factor (EGF) (as well as to 12-O-tetradecanoylphorbol-13-acetate (TPA)) by upregulation of M(r) 95,000 gelatinase (MMP-9) (M(r) 95K GL) and fibroblast-type collagenase (MMP-1) (FIB-CL), whereas control cells expressed barely detectable levels of either of these enzymes. The cells secreted 8-10 micrograms/10(6) cells/day (M(r) 95K GL) and 2-3 micrograms/10(6) cells/day (FIB-CL) of enzyme protein for at least 24 h when maximally induced. This level was attained only after a 24-h lag period, and the earliest emergence of enzyme protein in the culture medium required 10-14 h. IL-1 beta was by far the most potent cytokine with maximal effect already at 10(-10) M, whereas IL-1 alpha, TGF-alpha, and EGF required 20-100-fold higher concentrations. Pretreatment of the cells with TPA (10(-7) M) abolished the subsequent response to IL-1 beta, TGF-alpha, and EGF and at the same time resulted in > 90% reduction of cytosolic protein kinase C activity. Surprisingly, staurosporine, a potent kinase inhibitor, not only failed to block growth factor/cytokine responses but itself stimulated expression of the enzymes at a magnitude comparable to TPA. The inducing effect of TGF-alpha/EGF was down-regulated by 70-85% by 10(-7) M dexamethasone. Dexamethasone was less effective in ablating the IL-1 beta response yielding 60% reduction M(r) 95K GL and little or no reduction of FIB-CL. Dexamethasone also failed to block the TPA response.
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PMID:Interleukin-1 beta and transforming growth factor-alpha/epidermal growth factor induce expression of M(r) 95,000 type IV collagenase/gelatinase and interstitial fibroblast-type collagenase by rat mucosal keratinocytes. 839 30

Mononuclear cells isolated from sinusoid of rat liver by collagenase perfusion method showed a strong inhibitory effect on epidermal growth factor-stimulated proliferation of cocultured autologous hepatocytes, while mononuclear cells from peripheral blood and spleen did not. This inhibitory effect depended on the effector/target ratio. In a single-color flow cytometric analysis, about 25% of sinusoidal mononuclear cells consisted of asialo GM1+ natural killer cells, and there were relatively small numbers of CD3+ T cells and a few leukocyte common antigen-positive B cells compared to peripheral blood mononuclear cells. The natural killer cell activity of sinusoidal mononuclear cells was much stronger than that of peripheral blood mononuclear cells and splenic mononuclear cells. This activity was completely suppressed by the treatment with anti-asialo GM1 antibody plus complement. However, their inhibitory activity on proliferation of autologous hepatocytes was not affected by this treatment. These results suggest that the sinusoidal mononuclear cells, probably CD3+ T cells, play a role in regulation of autologous hepatocyte proliferation.
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PMID:Inhibition of epidermal growth factor-stimulated hepatocytes proliferation by autologous sinusoidal mononuclear cells in rat liver. 840 41

We demonstrated that four human oesophageal squamous cell carcinoma cell lines (TE8, TE9, TE10 and TE11) produced matrix metalloproteinase-1 (proMMP-1/tissue collagenase), 2 (ProMMP-2/'type IV collagenase'), 3 (proMMP-3/stromelysin), and 9 (proMMP-9/92-kDa gelatinase) as members of a matrix metalloproteinase (MMP) family, which degrades extracellular matrix macromolecules. Under normal culture conditions, in immunoblot analysis, proMMP-1 of M(r) = 53,00 was detected in one cell line (TE8), proMMP-2 of M(r) = 72,000 in three cell lines (TE9, TE10, and TE11), and proMMP-3 of M(r) = 57,000 in all four cell lines. In addition to these enzymes, in enzymography, a gelatinolytic activity around M(r) = 92-kDa, likely to be proMMP-9, was detected in only one cell line (TE10) under normal culture conditions. When these cell lines were treated with epidermal growth factor (EGF), however, the agent stimulated three cell lines (TE8, TE10 and TE11) to produce proMMP-9 in a dose-dose dependent manner. Oesophageal carcinoma-conditioned medium stimulated oesophageal fibroblasts to produce proMMP-1, -2, and -3, suggesting that the interaction between oesophageal carcinoma and stromal fibroblasts also plays a role in the production of MMPs by the latter. Our present study illustrates that oesophageal squamous cell carcinoma produces a variety of MMPs including proMMP-1, -2, -3, and -9 in vitro, suggesting that the ability of MMP production of the tumour may play an important role in its malignant behaviour and that the production of proMMP-9 may be regulated by EGF via overexpression of EGF receptors.
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PMID:Production of matrix metalloproteinase 9 (92-kDa gelatinase) by human oesophageal squamous cell carcinoma in response to epidermal growth factor. 847 29

Fibrotic reactions in the skin are frequently preceded by infiltration of inflammatory cells and subsequent migration of fibroblastic cells. Interleukin-1 is secreted by inflammatory cells and can regulate proliferation and protein synthesis of fibroblasts. Its role in fibroblast chemotaxis has not been elucidated in any detail. Using the well-established Boyden chamber assay for measurement of chemotaxis in vitro, we studied a wide range of recombinant human interleukin-1 alpha concentrations to assess intrinsic chemotactic activity of interleukin-1 alpha and to determine the capacity of this mediator to modify the chemotactic response of fibroblasts to other chemoattractants. This was compared with the interleukin-1 alpha dose required for enhancement of mRNA expression for collagenase. Although interleukin-1 alpha was not chemoattractive for fibroblasts, it specifically augmented migration toward fibroblast-conditioned medium and toward platelet-derived growth factor but not toward epidermal growth factor, fibronectin, or transforming-growth factor-beta. Interleukin-1 alpha did not measurably alter the expression of mRNA for the platelet-derived growth factor receptor or its platelet-derived growth factor-binding characteristics. Doses required to enhance fibroblast chemotaxis were distinctly lower than those required for stimulation of collagenase mRNA expression.
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PMID:Biphasic effects of interleukin-1 alpha on dermal fibroblasts: enhancement of chemotactic responsiveness at low concentrations and of mRNA expression for collagenase at high concentrations. 849 18

Cultured cells from the bovine endosalpinx were used to evaluate effects of estradiol-17 beta, progesterone, epidermal growth factor, and insulinlike growth factors I and II on [3H]thymidine incorporation. Cells were treated with hormones and growth factors when approximately 50% confluent. After 24 h, DNA synthesis was quantified by pulsing cells with [3H]thymidine for 12 h and determining uptake into DNA. Cells prepared by mechanical dispersal incorporated more [3H]thymidine than cells dispersed with collagenase. However, hormonal responses were the same for both types of cells. As compared to plastic, cells on a Matrigel substratum exhibited lower incorporation of [3H]thymidine and were unresponsive to hormones. Estradiol-17 beta increased [3H]thymidine incorporation slightly at 10(-10) mol/liter and higher. Epidermal growth factor, insulinlike growth factor-I, and insulinlike growth factor-II also stimulated [3H]thymidine incorporation. Effects of insulinlike growth factor-I were greater for cells treated with estradiol-17 beta. In the absence of estradiol, progesterone inhibited [3H]thymidine incorporation at 1, 10, and 100 ng/ml. When estradiol-17 beta was present, progesterone stimulated [3H]thymidine incorporation at 1 ng/ml and reduced incorporation at 100 ng/ml. In conclusion, [3H]thymidine incorporation by cultured oviductal endosalpingeal cells can be regulated by ovarian steroids and growth factors. These molecules may represent signals through which the ovary, embryo, and oviduct regulate oviductal growth.
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PMID:Steroidal and growth factor regulation of [3H]thymidine incorporation by cultured endosalpingeal cells of the bovine oviduct. 852 20


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