scholarly journals Production of matrix metalloproteinases by cultured bovine theca and granulosa cells

Reproduction ◽  
2005 ◽  
Vol 129 (1) ◽  
pp. 75-87 ◽  
Author(s):  
M F Smith ◽  
C G Gutierrez ◽  
W A Ricke ◽  
D G Armstrong ◽  
R Webb
Keyword(s):  
Matrix Metalloproteinases ◽  
Activity Patterns ◽  
Molecular Size ◽  
Conditioned Media ◽  
Gelatinolytic Activity ◽  
Gelatinase A ◽  
Thecal Cell ◽  
Mmp Inhibitor ◽  
Caseinolytic Activity ◽  
Granulosal Cells

Matrix metalloproteinases (MMPs) degrade the proteinaceous components of the extracellular matrix and are presumably essential for follicular growth culminating in ovulation or atresia. The objectives of this study were to characterize the gelatinolytic and caseinolytic MMPs secreted by cultured bovine thecal and granulosal cells and to determine the effect of luteinizing hormone (LH) on MMP secretion. Thecal and granulosal cells were collected from small bovine follicles (<5 mm) on day 2 or 5 of the estrous cycle (day 0 = estrus). A serum-free culture system was utilized in which bovine thecal and granulosal cells do not spontaneously luteinize, but produce androstenedione and estradiol in response to physiological concentrations of LH and follicle-stimulating hormone (FSH) respectively. The effect of LH (0, 1 or 100 ng/ml) on MMP production was determined in conditioned media collected every 48 h for 144 h. MMPs were detected by gelatin and casein zymography and MMP activity was quantified by image analysis. Thecal and granulosal cell conditioned media contained MMPs that had a relative molecular size (Mr) ranging from 53 000 to 200 000 and addition of 1,10 phenanthroline (MMP inhibitor) blocked gelatinolytic and caseinolytic activity. Patterns of gelatinolytic activity in thecal and granulosal cell conditioned media differed over time with theMr62 000 and 83 000 MMPs being increased (P< 0.05) and theMr53 000 MMP being decreased (P< 0.05) at 96 h of culture. LH (1 or 100 ng/ml) increased (P< 0.05) gelatinolytic activity of theMr53 000 and 62 000 gelatinases within thecal cell conditioned media but not granulosal cell conditioned media. TheMr62 000 and 83 000 gelatinolytic activities corresponded to the active forms of gelatinase A (Mr62 000) and B (Mr, 83 000) and gelatinase A was detected in thecal cell conditioned media by Western blot analysis. Caseinolytic activity (Mr83 000) was detected in both thecal and granulosal cell conditioned media and increased from 48 to 96 h. In summary, thecal and granulosal cells secrete gelatinolytic and caseinolytic MMPs and thecal cell production of gelatinase A was stimulated by LH.

Production of matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 by human brain tumors

1994 ◽  
Vol 81 (1) ◽  
pp. 69-77 ◽  
Author(s):  
Takao Nakagawa ◽  
Toshihiko Kubota ◽  
Masanori Kabuto ◽  
Kazufumi Sato ◽  
Hirokazu Kawano ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Matrix Metalloproteinases ◽  
Brain Tumors ◽  
Human Brain ◽  
Tumor Cells ◽  
Tumor Invasion ◽  
Gelatinolytic Activity ◽  
Normal Brain ◽  
Tissue Inhibitor Of Metalloproteinases ◽  
Human Brain Tumor

✓ The role of matrix metalloproteinases (MMP's) and their inhibitor, tissue inhibitor of metalloproteinases-1 (TIMP-1), in human brain tumor invasion was investigated. Gelatinolytic activity was assayed via gelatin zymography, and four MMP's (MMP-1, MMP-2, MMP-3, and MMP-9) and TIMP-1 were immunolocalized in human brain tumors and in normal brain tissues using monoclonal antibodies. The tissue was surgically removed from 44 patients: glioblastoma (five cases), anaplastic astrocytoma (six cases), astrocytoma (four cases), metastatic tumor (six cases), neurinoma (10 cases), meningioma (10 cases), and normal brain tissue (three cases). Glioblastomas, anaplastic astrocytomas, and metastatic tumors showed high gelatinolytic activity and positive immunostaining for MMP's; TIMP-1 was also expressed in these tumors, but some tumor cells were negative for the antibody. Astrocytomas had low gelatinolytic activity and the tumor cells showed no immunoreactivity for MMP's and TIMP-1. Although neurinomas and meningiomas had only moderate proteinase activity and exhibited positive immunoreactivity for MMP-9, intense expression of TIMP-1 was simultaneously observed in these tumor cells. These findings suggest that MMP's play an important role in human brain tumor invasion, probably due to an imbalance between the production of MMP's and TIMP-1 by the tumor cells.

scholarly journals Matrix Metalloproteinases Contribute to Brain Damage in Experimental Pneumococcal Meningitis

2000 ◽  
Vol 68 (2) ◽  
pp. 615-620 ◽  
Author(s):  
Stephen L. Leib ◽  
David Leppert ◽  
John Clements ◽  
Martin G. Täuber
Keyword(s):  
Matrix Metalloproteinases ◽  
Bacterial Meningitis ◽  
Brain Damage ◽  
Neuronal Injury ◽  
Housekeeping Gene ◽  
Close Correlation ◽  
Necrosis Factor Alpha ◽  
Mmp Inhibitor ◽  
Tnf Α ◽  
Cytokine Tumor Necrosis Factor

ABSTRACT The present study was performed to evaluate the role of matrix metalloproteinases (MMP) in the pathogenesis of the inflammatory reaction and the development of neuronal injury in a rat model of bacterial meningitis. mRNA encoding specific MMPs (MMP-3, MMP-7, MMP-8, and MMP-9) and the inflammatory cytokine tumor necrosis factor alpha (TNF-α) were significantly (P< 0.04) upregulated, compared to the β-actin housekeeping gene, in cortical homogenates at 20 h after infection. In parallel, concentrations of MMP-9 and TNF-α in cerebrospinal fluid (CSF) were significantly increased in rats with bacterial meningitis compared to uninfected animals (P = 0.002) and showed a close correlation (r = 0.76; P < 0.001). Treatment with a hydroxamic acid-type MMP inhibitor (GM6001; 65 mg/kg intraperitoneally every 12 h) beginning at the time of infection significantly lowered the MMP-9 (P< 0.02) and TNF-α (P < 0.02) levels in CSF. Histopathology at 25.5 ± 5.7 h after infection showed neuronal injury (median [range], 3.5% [0 to 17.5%] of the cortex), which was significantly (P < 0.01) reduced to 0% (0 to 10.8%) by GM6001. This is the first report to demonstrate that MMPs contribute to the development of neuronal injury in bacterial meningitis and that inhibition of MMPs may be an effective approach to prevent brain damage as a consequence of the disease.

Molecular regulation of cellular invasion— role of gelatinase A and TIMP-2

1996 ◽  
Vol 74 (6) ◽  
pp. 823-831 ◽  
Author(s):  
Anita E. Yu ◽  
Robert E. Hewitt ◽  
David E. Kleiner ◽  
William G. Stetler-Stevenson
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinases ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Gelatinase A ◽  
Cellular Mechanisms ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
The Matrix ◽  
Cell Matrix Interactions

Extracellular matrix (ECM) turnover is an event that is tightly regulated. Much of the coordinate (physiological) or discoordinate (pathological) degradation of the ECM is catalyzed by a class of proteases known as the matrix metalloproteinases (MMPs) or matrixins. Matrixins are a family of homologous Zn atom dependent endopeptidases that are usually secreted from cells as inactive zymogens. Net degradative activity in the extracellular environment is regulated by specific activators and inhibitors. One member of the matrixin family, gelatinase A, is regulated differently from other MMPs, suggesting that it may play a unique role in cell–matrix interactions, including cell invasion. The conversion from the 72 kDa progelatinase A to the active 62 kDa species may be a key event in the acquisition of invasive potential. This discussion reviews some recent findings on the cellular mechanisms involved in progelatinase A activation and, in particular, the role of tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) and transmembrane containing metalloproteinases (MT-MMP) in this process.Key words: tissue inhibitors of metalloproteinases, metalloproteinase, gelatinases, extracellular matrix, activation.

scholarly journals IL-12-mediated transcriptional regulation of matrix metalloproteinases

2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Eugenia Roupakia ◽  
Georgios S Markopoulos ◽  
Evangelos Kolettas
Keyword(s):  
Transcriptional Regulation ◽  
Matrix Metalloproteinases ◽  
Immune Responses ◽  
Nuclear Factor Κb ◽  
Interleukin 12 ◽  
Gelatinase A ◽  
Tissue Remodelling ◽  
Periodontal Ligament Fibroblasts ◽  
Protein Levels ◽  
Interstitial Collagenase

Matrix metalloproteinases (MMPs) are extracellular matrix (ECM) remodelling enzymes involved in developmental processes, tissue remodelling and repair, inflammatory and immune diseases and cancer. In a recent issue of Bioscience Reports (vol. 37, issue 6, BSR20170973), Liu and colleagues investigated the expression of MMPs such as MMP-1 (interstitial collagenase), MMP-3 (stromelysin 1) and MMP-13 (collagenase 3) in human periodontal ligament fibroblasts (hPDLFs) regulated by interleukin-12 (IL-12), a cytokine implicated in inflammatory and immune responses. They showed that IL-12 activates canonical nuclear factor-κB (NF-κB) signalling leading to increased expression of MMP-1, MMP-3 and MMP-13, and to a smaller reduction in the expression of MMP-2 (gelatinase A) and MMP-9 (gelatinase B) at both mRNA and protein levels, with corresponding changes in the secreted levels of these ECM-remodelling and immune regulatory metalloproteinases. While canonical NF-κB signalling regulates these MMPs, it also interacts with additional factors to determine whether some of these MMPs are induced or downregulated, in response to IL-12. Here, we comment on the possible mechanisms of IL-12-mediated transcriptional regulation of MMPs.

scholarly journals Role of Matrix Metalloproteinases 7 in the Pathogenesis of Laryngopharyngeal Reflux: Decreased E-cadherin in Acid exposed Primary Human Pharyngeal Epithelial Cells

2019 ◽  
Vol 20 (21) ◽  
pp. 5276 ◽  
Author(s):  
Nu-Ri Im ◽  
Doh Young Lee ◽  
Byoungjae Kim ◽  
Jian Kim ◽  
Kwang-Yoon Jung ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Culture Media ◽  
Laryngopharyngeal Reflux ◽  
Acid Exposure ◽  
Immunocytochemical Staining ◽  
Mmp Inhibitor ◽  
Transepithelial Permeability ◽  
Laryngopharyngeal Reflux Disease ◽  
E Cadherin

Cleavage of E-cadherin and the resultant weakness in the cell-cell links in the laryngeal epithelium lining is induced by exposure to acidic contents of the refluxate. Herein, we aimed to evaluate the role of matrix metalloproteinases (MMPs) in inducing E-cadherin level changes following acid exposure to the human pharyngeal mucosal cells. E-cadherin levels were inversely correlated with the duration of acid exposure. Treatment with actinonin, a broad MMP inhibitor, inhibited this change. Immunocytochemical staining and transepithelial permeability test revealed that the cell surface staining of E-cadherin decreased and transepithelial permeability increased after acid exposure, which was significantly inhibited by the MMP inhibitor. Among the various MMPs analyzed, the mRNA for MMP-7 in the cellular component was upregulated, and the secretion and enzymatic activity of MMP-7 in the culture media increased with the acid treatment. Consequently, MMP-7 plays a significant role in the degradation of E-cadherin after exposure to a relatively weak acidic condition that would be similar to the physiologic condition that occurs in Laryngopharyngeal reflux disease patients.

Abstract WP298: Matrix Metalloproteinases Are Involved In The Regulation Of Angiogenesis After Intracerebral Hemorrhage

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Qi-Ting Liu ◽  
Han-Jin Cui ◽  
Jie-Kun Luo ◽  
Yuan Lin ◽  
TAO TANG
Keyword(s):  
Matrix Metalloproteinases ◽  
Intracerebral Hemorrhage ◽  
Western Blot ◽  
Sham Group ◽  
Treated Group ◽  
Barrier Dysfunction ◽  
Mmp Inhibitor ◽  
Neurological Severity Score ◽  
Mmp9 Expression ◽  
The Times

Background and purpose: Intracerebral hemorrhage (ICH) is one of the most devastating subtypes of stroke. And our previous work has demonstrated that ICH induces angiogenesis, accompanied by up-regulation of pro-angiogenic factors. Matrix metalloproteinases (MMPs) can cause blood-brain barrier dysfunction by degrading the extracellular cellular matrix (ECM) around the vessels after ICH, but opening a way for the prolonging newborn vessels is a key step for their functional structure, therefore, the purpose of the study is to investigate whether MMPs are involved in the process of angiogenesis after ICH. Methods: Thirty Kunming mice were randomly divided into sham group, ICH group and doxycycline (DOX)-treated group. And then 5 mice were randomly selected for Western Blot to detect the expression of MMP9, and the other five for the immunohistochemistry to detect vWF. ICH model was induced by injection collagenase type VII into right globus pallidus stereotaxically, and DOX, a broad-spectrum MMP inhibitor, was injected by intraperitoneally at 7 days after ICH induction. Neurological severity score (NSS), corner turn test and foot-fault test were used to investigate the neurological function. And vWF-positive vessels were counted around the hematoma. Results: At 7 days, there is no difference between the two ICH-induced groups in NSS, corner turn test, foot-fault test; while at 14 days, the NSS in ICH group is significantly lower than that of DOX-treated group ( P <0.05), and the times for right-turn and foot-fault in ICH group are notably fewer than those of DOX-treated group ( P <0.05); At 14d, the number of vWF-postive microvessel in ICH group was significantly larger than that of DOX-treated group ( P <0.01), and Western Blot revealed that DOX decreased MMP9 expression remarkably( P <0.01). Conclusion: Matrix metalloproteinases were involved in the regulation of angiogenesis after ICH.

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