共查询到20条相似文献,搜索用时 15 毫秒
1.
Akio Sakamoto Yoshinao Oda Yukihide Iwamoto Masazumi Tsuneyoshi 《Journal of cancer research and clinical oncology》1999,125(10):541-548
Membrane type 1 matrix metalloproteinase (MT1-MMP) has been identified as an activator of the proenzyme of matrix metalloproteinase
2 (MMP-2: gelatinase A), and has also been shown to play a crucial role in tumor invasion by activating proMMP2 in both lung
and gastric carcinoma. The tissue inhibitor of metalloproteinase 2 (TIMP-2) plus the MT1-MMP complex also plays an important
role in the activation of proMMP-2. In this study, the expressions of MT1-MMP, MMP-2 and TIMP-2 were evaluated in 10 enchondromas,
34 conventional chondrosarcomas, 5 clear-cell chondrosarcomas, 7 mesenchymal chondrosarcomas and 8 dedifferentiated chondrosarcomas.
The expressions were immunohistochemically visualized on paraffin sections and the levels of expression were assessed semiquantitatively.
The extent of staining was assessed by the extent score in order to determine the overall level of expression. The extent
scores of MT1-MMP, MMP-2 and TIMP-2 in grade 2 chondrosarcoma were significantly higher than those in either enchondroma or
grade 1 chondrosarcoma (P < 0.05). In conventional chondrosarcoma, significant correlations were found between the extent scores of MT1-MMP and MMP-2
(P < 0.001), MT1-MMP and TIMP-2 (P < 0.01), and MMP-2 and TIMP-2 (P < 0.01). The undifferentiated small round tumor cells of mesenchymal chondrosarcoma showed lower positive rates and extent
scores for MT1-MMP (2/7, 0.7 ± 0.5) and MMP-2 (3/7, 0.7 ± 0.4) than for cartilaginous components of mesenchymal chondrosarcoma
[MT1-MMP (4/7, 1.3 ± 0.5) and MMP-2 (7/7, 1.9 ± 0.3)] or conventional chondrosarcoma. In dedifferentiated chondrosarcoma,
the extent scores of MT1-MMP, MMP-2 and TIMP-2 in low-grade cartilaginous components were not significantly different from
those in conventional chondrosarcoma; however, the high-grade anaplastic components showed high extent scores for MT1-MMP,
MMP-2 and TIMP-2, compared with the low-grade cartilaginous components of dedifferentiated chondrosarcoma or conventional
chondrosarcoma. According to our results, the expression of MT1-MMP as well as that of MMP-2 or TIMP-2 demonstrated a significant
correlation with the tumor grade in human cartilaginous tumors. Furthermore, the expressions of MT1-MMP, MMP-2 and TIMP-2
were also found to play a crucial role in invasion in the high-grade components of dedifferentiated chondrosarcoma.
Received: 17 February 1999 / Accepted: 21 April 1999 相似文献
2.
Schram K Wong MM Palanivel R No EK Dixon IM Sweeney G 《Journal of molecular and cellular cardiology》2008,44(5):874-881
Myocardial matrix remodeling is a well-recognized disease modifier in the pathogenesis of heart failure, although the precise underlying molecular mechanisms remain to be elucidated. Here we investigated the effects of leptin, circulating levels of which are typically increased in obese individuals, on MMP and collagen expression and MMP activity in isolated cardiac myofibroblasts. Neonatal rat myofibroblasts were treated with 6 nM recombinant leptin and the collected supernatant analyzed for MMP-2 activity via gelatin zymography. MMP-2, MT1-MMP and procollagen-I and -III protein expression were determined by western blotting and MMP-2 and MT1-MMP mRNA expression were examined utilizing real-time PCR. Procollagen-I levels were analyzed by confocal microscopy and collagen synthesis was determined through [3H]-proline incorporation. Exposure of myofibroblasts to leptin (24 h) significantly increased MMP-2 activity, while mRNA and protein levels remained unchanged. Leptin also significantly enhanced mRNA and protein expression of MT1-MMP, a known activator of MMP-2. Biotinylation assays indicated increased cell surface expression of MT1-MMP in response to leptin and use of a MT1-MMP inhibitor attenuated the leptin-mediated elevation of MMP-2 activity. Total cellular collagen synthesis was unaffected by leptin treatment, however intracellular procollagen-I protein was significantly increased in treated cells. Furthermore, extracellular soluble procollagen-I was increased, while a decrease in soluble procollagen-III protein was observed in conditioned media. In summary, these findings in isolated cardiac myofibroblasts support the suggestion that leptin may directly influence myocardial matrix metabolism, and this may represent a mechanism contributing to cardiac fibrosis in obese patients with elevated plasma leptin levels. 相似文献
3.
Koyama S 《Journal of cancer research and clinical oncology》2005,131(12):809-814
Purpose:The crucial role of tumor stroma in cancer cell invasion has been described in human carcinoma tissues. However, myofibroblastic
invasion remains largely unexplored in malignant ascites. Purpose of this study is to investigate the spatial localization
or regulation of matrix metalloproteinases (MMP-2, -7 -9, MT1-MMP) and their inhibitors (TIMP-2 and -4) on myofibroblasts
from malignant ascites in 20 patients with gastric carcinoma. Methods: The quantitative flow cytometric analysis of MMPs or TIMPs on myofibroblasts was based on the percentage of double positive
cells defined by anti MMPs or anti TIMPs, and anti α-smooth muscle actin (α-SMA) antibodies. Result: The results clearly showed that the coordination of the high level of cell-surface expression of secreted MMPs and TIMPs
was noted on the α-SMA+ myofibroblasts. The finding suggests the possible formation of ternary complex, MT1-MMP/TIMPs/MMPs on the cells. The events
might be a cause and result of activation processing of MMPs on the cells. Conclusion: This study provides the presence of invasive myofibroblasts with activated MMPs in close association with MMPs+ and TIMPs+ cancer cells and tumor-infiltrating lymphocytes from malignant ascites, emphasizing the importance of molecular cross-talk
in tumor-host microenvironment for cancer invasion, metastasis and progression. 相似文献
4.
Apoptosis of human hepatic myofibroblasts promotes activation of matrix metalloproteinase-2 总被引:9,自引:0,他引:9
Liver fibrosis is potentially reversible after removal of the injurious agent. Fibrosis resolution is characterized by apoptosis of hepatic myofibroblasts and degradation of extracellular matrix components. Matrix metalloproteinase-2 (MMP-2) is involved in matrix remodeling. In the liver, it is synthesized by myofibroblasts, secreted as a proenzyme, and activated by membrane type-MMPs (MT-MMP) such as MT1-MMP. The goal of this work was to determine whether apoptosis induction in human hepatic myofibroblasts modulates the gene expression of MMP-2 and/or its activation by MT1-MMP. Induction of apoptosis by cytochalasin D or C(2)-ceramide did not modulate MMP-2 mRNA expression. In contrast, apoptosis was associated with marked activation of pro-MMP-2, as shown by gelatin zymography, which revealed the presence of the 59-kd active form, whereas untreated cells only expressed the 66-kd proform. SB-203580, a specific inhibitor of p38 (MAPK), selectively abrogated both C(2)-ceramide-induced apoptosis and pro-MMP-2 activation. Apoptosis-induced pro-MMP-2 activation was inhibited by the tissue inhibitors of metalloproteinases (TIMP)-2 but not by TIMP-1, implying involvement of an MT-MMP-mediated process. Induction of apoptosis by cytochalasin D and C(2)-ceramide upregulated MT1-MMP protein expression and MT1-MMP mRNA expression. In conclusion, apoptosis of hepatic myofibroblasts induces pro-MMP-2 activation through increased MT1-MMP expression. HEPATOLOGY 2002;36:615-622.) 相似文献
5.
Glycation cross-links inhibit matrix metalloproteinase-2 activation in vascular smooth muscle cells cultured on collagen lattice 总被引:4,自引:0,他引:4
Aims/hypothesis. Extracellular matrix glycation has been proposed to contribute to the arterial stiffness observed in aging and diabetes.
We examined whether matrix protein glycation regulates the proleolytic process through the manipulation of matrix metalloproteinases
(MMPs) activation, using collagen fibrils model. Methods. Vascular smooth muscle cells were cultured on control or glycated collagen fibrils. Matrix metalloproteinase-2 activation
and the production of tissue inhibitors of metalloproteinase (TIMPs) were measured in the conditioned medium by using gelatin
zymography and immunoblotting. Membrane type 1 matrix metalloproteinase (MT1-MMP) expression was also measured in cell lysates.
Results. When smooth muscle cells were cultured on collagen fibrils, pro-MMP-2 processing to active form was observed in the conditioned
medium in coincidence with the increased MT1-MMP expression and the suppressed TIMP-2 production. Culturing smooth muscle
cells on glycated collagen fibrils inhibited MMP-2 activation and attenuated MT1-MMP expression without the alteration of
TIMP-2 production compared with control fibrils, indicating the possible mechanism of the suppression of MT1-MMP expression
for the inhibition of MMP-2 activation on glycated collagen fibrils. Inclusion of aminoguanidine, an inhibitor of cross-linking
formation, during collagen glycation restored the MMP-2 activation, suggesting the role of cross-links on the inhibition of
MMP-2 activation. Conclusion/interpretation. These observations suggest that glycation-induced cross-linking formation in interstitial collagen contributes to arterial
stiffness in aging and diabetes through the manipulation of matrix metalloproteinase activation along with the reduction of
the susceptibility to proteolytic enzymes. [Diabetologia (2001) 44: 433–436]
Received: 16 October 2000 and in revised form: 18 December 2000 相似文献
6.
7.
Induction of membrane-type matrix metalloproteinase-1 stimulates angiogenic activities of bovine aortic endothelial cells 总被引:2,自引:0,他引:2
Matrix metalloproteinases (MMPs) have been reported to play critical roles in endothelial cell migration and matrix remodeling
during the angiogenic process. Among these MMPs, membrane-type MMP-1 (MT1-MMP) is an important molecule that can trigger the
invasion of tumor cells by activating MMP-2 on their plasma membrane. However, the precise involvement of MT1-MMP in the angiogenic
process has not been determined. To investigate the roles of the MT1-MMP by the matrix remodeling of endothelial cells, MT1-MMP
expression vector was transfected into bovine aortic endothelial cells (BAECs). Increased expression of MT1-MMP in BAECs enhanced
the activation of MMP-2, invasion and migration of BAECs. Moreover, the capacity of tube formation was increased in MT1-MMP
transfectants. However, cotransfection with antisense MT1-MMP expression vector abolished the effects of MT1-MMP overexpression.
These observations indicate that MT1-MMP is involved in the angiogenic process of endothelial cells in vitro.
This revised version was published online in June 2006 with corrections to the Cover Date. 相似文献
8.
9.
Liao EY Liao HJ Guo LJ Zhou HD Wu XP Dai RC Luo XH 《Journal of endocrinological investigation》2004,27(1):1-5
Our previous study showed that estrogen stimulates membrane-type matrix metalloproteinases-1 (MT1-MMP) production in osteoblastic cells culture, but has no effect on MMP-2 and TIMP-2 synthesis. Osteoblast-derived MT1-MMP have been recently implied to play a role in bone metabolism by degrading tumor necrosis factor-alpha (TNF-alpha), resolving extracellular matrix and activating proMMP-2, which requires the process of activation mediated by MT1-MMP/tissue inhibitor of metalloproteinase (TIMP-2) complex on the cell surface. To investigate the mechanism of bone loss following estrogen deficiency, we examined the effects of estrogen on osteoblast synthesis of MT1-MMP, MMP-2 and TIMP-2. In situ hybridization and immunohistochemistry of rat bone samples were used to document the synthesis of MT1-MMP, MMP-2, and TIMP-2 mRNA and protein. Osteoblasts from distal femoral head showed an increase in the pattern of MT1-MMP mRNA and protein production in sham-operated controls and 17beta-estradiol (E2)-treated rats, compared with the ovariectomized group; the synthesis of MMP-2 and TIMP-2 mRNA and protein was unaffected. Our data show a down-regulation of MT1-MMP synthesis by osteoblast in vivo following estrogen withdrawal, and treatment with E2 resulted in induced MT1-MMP expression in vivo. There is evidence suggesting a role for MT1-MMP in the process of bone loss during the pathogenesis of osteoporosis. 相似文献
10.
Cardiac rupture is a fatal complication of myocardial infarction (MI); however, its underlying molecular mechanisms are not
fully understood. This study investigated the role of tissue inhibitor of metalloproteinase-3 (TIMP-3)/matrix metalloproteinase
(MMP)/epidermal growth factor (EGF)/transforming growth factor (TGF)-β1 pathway in infarct healing and effects of cetuximab
on cardiac rupture after MI. Induction of MI was achieved by left coronary artery ligation in wild-type (WT) and TIMP-3−/− mice. TIMP-3 deficiency resulted in a fourfold increase in cardiac rupture and 50% decrease in survival after MI. Hydroxyproline
content, collagen synthesis and myofibroblast cell number in the infarct region, and the force required to induce rupture
of the infarct scar were significantly decreased, while MMP activity was increased in TIMP-3−/− mice. EGF proteins were increased by threefold in TIMP-3−/− mice following MI, while TGF-β1 mRNA levels were decreased by 68%. Cell proliferation of cultured adult cardiac myofibroblasts
was significantly decreased in TIMP-3−/− compared to WT myofibroblasts. EGF treatment significantly decreased collagen synthesis and TGF-β1 expression. Conversely,
TGF-β1 treatment increased collagen synthesis in cardiac myofibroblasts. Treatment with cetuximab significantly decreased
the incidence of cardiac rupture and improved survival post-MI in TIMP-3−/− mice. We conclude that deficiency in TIMP-3 increases cardiac rupture post-MI via EGF/epidermal growth factor receptor (EGFR)
signaling which downregulates TGF-β1 expression and collagen synthesis. Inhibition of EGFR by cetuximab protects against cardiac
rupture and improves survival post-MI. 相似文献
11.
Matrix metalloproteinase (MMP) expression by differentiated thyroid carcinoma of children and adolescents 总被引:4,自引:0,他引:4
Patel A Straight AM Mann H Duffy E Fenton C Dinauer C Tuttle RM Francis GL 《Journal of endocrinological investigation》2002,25(5):403-408
The factor(s) that control metastasis of thyroid carcinoma are unknown, but the matrix metalloproteinases (MMPs) are excellent candidates. MMP-1, membrane-type-1 MMP (MT1-MMP), and tissue inhibitor of MMP-1 (TIMP-1) have all been implicated, but the site of production and importance are disputed. In vitro, normal thyroid cells secrete TIMP-1, while thyroid cancer cells secrete TIMP-1 and MMP-1. However, previous pathological studies identified MMP-1 and TIMP-1 only in the stroma surrounding thyroid carcinoma. These data suggest that thyroid carcinoma or tumor-associated inflammatory cells might secrete a factor(s) which stimulates MMP-1 or TIMP-1 expression by surrounding tissues. We hypothesized that MMP-1, MT1-MMP, and TIMP-1 would be directly expressed by thyroid carcinoma and might promote invasion or metastasis. We used immunohistochemistry to determine the expression of MMP-1, MT1-MMP, and TIMP-1 in 32 papillary thyroid carcinoma (PTC), 10 follicular thyroid carcinoma (FTC) and 13 benign thyroid lesions from children and adolescents. The intensity of staining was graded from absent (grade 0) to intense (grade 3). Average MMP-1 expression (mean relative intensity units+/-SE) was significantly greater among PTC (1.97+/-0.15; p=0.004) and FTC (2.2+/-0.25; p=0.006) compared to benign lesions (1.30+/-0.15); but there was no relationship between MMP-1 expression and invasion, metastasis, or recurrence. Expression of MT1-MMP and TIMP-1 was similar for benign and malignant lesions; but recurrent PTC expressed lower levels of TIMP-1 when compared to non-recurrent PTC (p=0.049). Only the expression of TIMP-1 correlated with the presence of tumor-associated lymphocytes (r=0.35, p=0.032). We conclude that MMP-1, MT1-MMP and TIMP-1 are all expressed by thyroid carcinoma and could be important in promoting recurrence. 相似文献
12.
TIMP-2、MMP-2和MT1-MMP在活化肝星状细胞中的表达及对细胞外基质合成分泌的影响 总被引:1,自引:0,他引:1
目的 研究金属蛋白酶组织抑制剂-2(TIMP-2)、基质金属蛋白酶-2(MMP-2)和膜型基质金属蛋白酶-1(MT1-MMP)在活化肝星状细胞(HSCs)中的表达,观察其对细胞外基质(ECM)合成分泌的影响.方法 原代分离培养大鼠HSCs活化后,分别给予40~160 pmol化学合成经修饰抗TIMP-2 siRNA进行干预,检测培养细胞上清液透明质酸(HA)、Ⅲ型前胶原(PCⅢ)和羟脯氨酸(Hyp)的含量,采用荧光实时定量PCR法检测TIMP-2、MMP-2、MT1-MMP、MMP-13、COL Ⅰ和COL Ⅲ mRNA的表达,western印迹检测TIMP-2、MT1-MMP和MMP-13蛋白表达及明胶酶谱法检测MMP-2蛋白表达.结果 应用化学合成经修饰抗TIMP-2 siRNA后,TIMP-2、MMP-2、MT1-MMP、COL Ⅰ和COL Ⅲ的表达明显降低,而MMP-13的表达则明显增加,培养细胞上清液中HA、PCⅢ和Hyp的含量也明显减少.结论 TIMP-2通过MT1-MMP介导MMP-2的活化,抑制TIMP-2的表达,MT1-MMP和MMP-2的表达随之降低,而HSCs合成分泌ECM也相应减少. 相似文献
13.
Nibedita Chattopadhyay Aparna Mitra Eva Frei Amitava Chatterjee 《Journal of cancer research and clinical oncology》2001,127(11):653-658
PURPOSE: Integrins are transmembrane heterodimeric molecules that mediate cellular adhesion and are involved in different biological processes, such as tumor development and invasion of tumor cells. Matrixmetalloproteases (MMP) are a family of secreted or membrane proteins capable of digesting extracellular matrix. It has been shown that MMP-2 binds to alphavbeta3 integrin. Recent evidence suggests that a complex of membrane-type MMP (MT1-MMP) and tissue inhibitor of metalloptroteinase-2 (TIMP-2) participate in the activation of alphavbeta3-associated MMP-2. We investigated whether alphavbeta3 and MMP-2 are associated on the membranes of a human cell line, SiHa, and the possible involvement of MT1-MMP and TIMP-2 in the modulation of MMP-2 activity. METHODS: Immunoprecipitation of SiHa membrane extracts with monoclonal antibodies against alphav or MMP-2, and western blots of immunoprecipitates and serum-free conditioned media were performed. TIMP-2 in conditioned medium and MT1-MMP in the membrane fraction was assayed by western blot. Zymography of anti-alphav antibody immunoprecipitates and conditioned media were used to show gelatinolytic activity. RESULTS: The coprecipitation of MMP-2 with alphavbeta3 by anti-alphav antibody is a strong indication that SiHa cell surface alphavbeta3 integrin is a receptor for MMP-2. Immunoblot assays show the expression of MT1-MMP on SiHa cell membranes and secreted TIMP-2 and pro-MMP-2 in the medium. CONCLUSIONS: SiHa cells express all the molecules which are reported to form a complex to activate pro-MMP-2. Active MMP-2 associated with alphavbeta3 may regulate matrix degradation and thereby modulate directed motility of SiHa cells. 相似文献
14.
High glucose concentration inhibits the expression of membrane type metalloproteinase by mesangial cells: possible role in mesangium accumulation 总被引:28,自引:0,他引:28
Aims/hypothesis. High glucose concentration decreases the degradation of mesangium matrix, an action substantially mediated by a reduction
in the activities of the matrix metalloproteinases (MMPs). Metalloproteinase-2 is unique in that it is activated on the cell
surface by one of the membrane type metalloproteinases (MT1-MMP), a process involving complex interactions with tissue inhibitor
of metalloproteinase-2. The aim of this study was investigate the effects of glucose concentration on mesangial cell gene
expression of MT1-MMP and its ability to modulate the activation of metalloproteinase-2. Methods. Gene expression was determined using competitive RT-PCR, protein expression of MMP-2 was measured by western blot and its
activation by zymography. Concanavalin A, known to increase MT1-MMP expression was added in some experiments. Results. High glucose concentration decreased MT1-MMP gene expression (11.52 ± 1.63 and 4.84 ± 0.72 amol/μg RNA, 5 vs 25 mmol/l glucose, respectively) and decreased activation
of MMP-2 by 30 % despite a twofold increase in gene expression of MMP-2. Concanavalin A increased expression of MT1-MMP and activation of MMP-2. Irrespective of whether MMP-2 was from endogenous or exogenous source there was an excellent correlation
between the MT1-MMP expression and degree of MMP-2 activation, whereas the gene expression of TIMP-2 was not significantly altered by high glucose
concentration or concanavalin A. Conclusions/interpretation. Our results indicate that in a high glucose milieu, suppression of MT1-MMP expression could explain the low MMP-2 activity in the presence of high MMP-2 expression. This process could contribute to the mesangium matrix accumulation in diabetic nephropathy. [Diabetologia (2000)
43: 642–648]
Received: 18 November 1999 and in revised form: 17 January 2000 相似文献
15.
16.
MMP-2, MT1-MMP, and TIMP-2 are essential for the invasive capacity of human mesenchymal stem cells: differential regulation by inflammatory cytokines 总被引:22,自引:0,他引:22
Human mesenchymal stem cells (hMSCs) represent promising tools in various clinical applications, including the regeneration of injured tissues by endogenous or transplanted hMSCs. The molecular mechanisms, however, that control hMSC mobilization and homing which require invasion through extracellular matrix (ECM) barriers are almost unknown. We have analyzed bone marrow-derivedhMSCs and detected strong expression and synthesis of matrix metalloproteinase 2 (MMP-2), membrane type 1 MMP (MT1-MMP), tissue inhibitor of metalloproteinase 1 (TIMP-1), and TIMP-2. The ability of hMSCs to traverse reconstituted human basement membranes was effectively blocked in the presence of synthetic MMP inhibitors. Detailed studies by RNA interference revealed that gene knock-down of MMP-2, MT1-MMP, or TIMP-2 substantially impaired hMSC invasion, whereas silencing of TIMP-1 enhanced cell migration, indicating opposing roles of both TIMPs in this process. Moreover, the inflammatory cytokines TGF-beta1, IL-1beta, and TNF-alpha up-regulated MMP-2, MT1-MMP, and/or MMP-9 production in these cells, resulting in a strong stimulation of chemotactic migration through ECM, whereas the chemokine SDF-1alpha exhibited minor effects on MMP/TIMP expression and cell invasion. Thus, induction of specific MMP activity in hMSCs by inflammatory cytokines promotes directed cell migration across reconstituted basement membranes in vitro providing a potential mechanism in hMSC recruitment and extravasation into injured tissues in vivo. 相似文献
17.
Tumor necrosis factor alpha induces human atrial myofibroblast proliferation, invasion and MMP-9 secretion: inhibition by simvastatin 总被引:6,自引:0,他引:6
OBJECTIVE: Tumor necrosis factor alpha (TNFalpha) is implicated in myocardial remodeling, a process in which activated cardiac fibroblasts (myofibroblasts) secrete matrix-degrading metalloproteinases (MMPs) and undergo increased proliferation and invasion. Statins are cholesterol-lowering drugs that also have direct cellular effects, which may underlie their ability to reduce myocardial remodeling. This study investigated the effect of TNFalpha on human cardiac myofibroblast proliferation, invasion and MMP-9 secretion, and determined whether these properties were modulated by simvastatin. METHODS: Human cardiac myofibroblasts were cultured from right atrial appendage. TNF receptor expression was quantified by immunoblotting. Cell proliferation, invasion, MMP-9 secretion and MMP-9 mRNA expression were determined by cell counting, Matrigel-coated modified Boyden chamber assays, gelatin zymography and RT-PCR, respectively. RESULTS: Human atrial myofibroblasts expressed the TNF-RI and TNF-RII receptor subtypes. TNFalpha (1 ng/ml) induced a 23.1+/-3.9% increase in cell number after 4 days (P<0.001). Additionally, TNFalpha (1-10 ng/ml) significantly (P<0.01) increased myofibroblast invasion, with a concomitant increase in MMP-9 secretion, that was due to increased MMP-9 mRNA levels. Using TNF-R-specific neutralizing antibodies, we determined that these cellular effects of TNFalpha were predominantly TNF-RI-mediated. Simvastatin (0.1-10 mumol/l) concentration dependently inhibited TNFalpha-induced myofibroblast proliferation, invasion and MMP-9 secretion. CONCLUSIONS: TNFalpha, acting predominantly via the TNF-R1 receptor, increased human atrial myofibroblast proliferation, invasion and MMP-9 secretion, all of which were inhibited by simvastatin. Inhibition of cytokine-induced cardiac myofibroblast activation by statins provides a rationale for their use in patients with cardiac pathologies characterized by adverse myocardial remodeling. 相似文献
18.
Effects of hypoxia, hyperoxia on the regulation of expression and activity of matrix metalloproteinase-2 in hepatic stellate cells 总被引:11,自引:0,他引:11
Chen PS Zhai WR Zhou XM Zhang JS Zhang YE Ling YQ Gu YH 《World journal of gastroenterology : WJG》2001,7(5):647-651
AIM To study the effects of hypoxia,hyperoxia on theregulation of expression and activity of matrixmetalloproteinase-2 (MMP-2) in hepatic stellate cells(HSC).METHODS The expressions of MMP-2,tissue inhibitor ofmatrix metalloproteinass-2 (TIMP-2) and membrane typematrix matalloproteinass-1 (MT1-MMP) in cultured rat HSCwere detected by immunocytochemistry (ICC) and in situhybridization (ISH).The contents of MMP-2 and TIMP-2 inculture supernatant were detected with ELISA and theactivity of MMP-2 in supernatant was revealed byzymography.RESULTS In the situation of hypoxia for 12h,theexpression of MMP-2 protein was enhanced (hypoxiagroup positive indexes:5.7±2.0,n=10;control:3.2±1.0,n=7;P<0.05),while TIMP-2 protein was decreasedin HSC (hypoxla group positive indexes:2.5±0.7,n=10;control:3.6±1.0,n=7;P<0.05),and the activity(total A) of MMP-2 in suparnatant declined obviously(hypoxla group:7.334±1.922,n=9;control:17.277±7.424,n=11;P<0.01).Compared the varied duration ofhypoxia,the changes of expressions Including mRNA andprotein level as well as activity of MMP-2 were mostnotable in 6 h group.The highest value (Ahypoxla~-Acontrol) ofthe protein and the most intense signal of mRNA were inthe period of hypoxia for 6 h,along with the lowestactivity of MMP-2.In the situation of hyparoxia for 12 h,the contents (A_(450)) of MMP-2 and TIMP-2 in supernatantwere both higher than those in the control,especially theTIMP-2 (hyperoxla group:0.0499±0.0144,n=16;control:0.0219±0.0098,n=14;P<0.01),and so wasthe activity of MMP-2 (hyperoxia group:5.252±0.771,n=14;control:4.304±1.083,n=12;P<0.05),and the expression of MT1-MMP was increased.CONCLUSION HSC is sensitive to the oxygen,hypoxiaenhances the expression of MMP-2 and the effect is moremarked at the early stage;hyperoxia mainly raises theactivity of MMP-2. 相似文献
19.
Schwandner O Schlamp A Broll R Bruch HP 《International journal of colorectal disease》2007,22(2):127-136