scholarly journals Differential regulation of matrix metalloproteinases and their inhibitors in human glomerular epithelial cells in vitro.

1998 ◽  
Vol 9 (9) ◽  
pp. 1629-1637
Author(s):  
J Martin ◽  
R Steadman ◽  
J Knowlden ◽  
J Williams ◽  
M Davies
Keyword(s):  
Epithelial Cells ◽  
Matrix Metalloproteinases ◽  
Specific Inhibitor ◽  
Differential Regulation ◽  
Dependent Manner ◽  
Gelatinase A ◽  
Type Iv Collagenase ◽  
Gelatinase B ◽  
Type Iv ◽  
Glomerular Epithelial Cells

The present study examines the effect of transforming growth factor-beta1 (TGF-beta1) and interleukin-1beta (IL-1beta) on the regulation of gelatinase A, gelatinase B, tissue inhibitor of metalloproteinase-I (TIMP-I) and TIMP-II in human glomerular epithelial cells (GEC). The addition of TGF-beta1 resulted in the increased production and secretion of both gelatinase A (72-kD type IV collagenase) and gelatinase B (92-kD type IV collagenase), in a dose- and time-dependent manner. In contrast, the addition of IL-1beta to GEC resulted in the stimulation of secretion of gelatinase B but not gelatinase A. When the secretion of the regulatory inhibitors was examined, IL-1beta or TGF-beta1 both resulted in an increased secretion of TIMP-I, whereas the secretion of TIMP-II was downregulated. Such results demonstrate an independent and opposite regulation of the enzymes and their inhibitors. Of particular interest was the observation of the differential regulation of gelatinase A and its specific inhibitor TIMP-II (which binds to the latent form of this enzyme) in response to TGF-beta1. These results for the first time indicate that in human GEC, matrix metalloproteinases (MMP), as well as their specific inhibitors, are independently regulated by different cytokines. MMP and their regulatory tissue inhibitors (TIMP) play an important role in tissue remodeling. The results of the present study serve to emphasize both the complex regulation of matrix metabolism in the glomerulus and the potential pathologic role of an imbalance between the proteinases and their inhibitors in various forms of glomerular disease.

scholarly journals Glomerular epithelial cells secrete a glomerular basement membrane-degrading metalloproteinase.

1992 ◽  
Vol 2 (9) ◽  
pp. 1388-1397
Author(s):  
R Johnson ◽  
H Yamabe ◽  
Y P Chen ◽  
C Campbell ◽  
K Gordon ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Type Iv Collagen ◽  
Dependent Manner ◽  
Type Iv Collagenase ◽  
Glomerular Diseases ◽  
Major Band ◽  
Type Iv ◽  
Glomerular Epithelial Cells

Cultured rat glomerular epithelial cells (GEC) were examined for their ability to release extracellular matrix-degrading proteinases with [3H]gelatin as substrate. GEC-conditioned media, under serum-free conditions, contained modest amounts of gelatinase activity (1 to 10 U/mg of protein); the activity was maximal at neutral pH, was inhibited by zinc chelators, was not inhibited by tissue inhibitor of metalloproteinase-2, and could not be further activated by trypsin or organomercurials. Gelatin substrate sodium dodecyl sulfate-polyacrylamide gels of GEC-conditioned medium revealed several zones of lysis, with molecular sizes of 150 kd (major band), and 220, 86 to 93, and 52 to 54 kd (minor bands). Northern blot analysis demonstrated that the GEC metalloproteinase(s) were distinct from the 68- to 72-kd type IV collagenase/gelatinase present in mesangial cells or the 92-kd type IV collagenase present in neutrophils. The GEC gelatinolytic activity also degraded insoluble type IV collagen in glomerular basement membrane in a dose-dependent manner. The major metalloproteinase activity responsible for the type IV collagen degradation has a molecular size of 150 kd with a type IV collagen substrate gel. Thus, GEC produce several neutral metalloproteinases, which, by virtue of their substrate specificity, may play an important role in glomerular basement membrane remodeling and in glomerular diseases characterized by alterations in basement membrane permeability.

scholarly journals Proteolytic Cascade Enzymes Increase in Focal Cerebral Ischemia in Rat

1996 ◽  
Vol 16 (3) ◽  
pp. 360-366 ◽  
Author(s):  
Gary A. Rosenberg ◽  
Milo Navratil ◽  
Frank Barone ◽  
Giora Feuerstein
Keyword(s):  
Focal Cerebral Ischemia ◽  
Vasogenic Edema ◽  
Artery Occlusion ◽  
Tissue Type ◽  
Intracerebral Injection ◽  
Gelatinase A ◽  
Type Iv Collagenase ◽  
Gelatinase B ◽  
Type Iv ◽  
Wistar Kyoto

Cerebral infarction initiates a cascade of molecular events, leading to proteolytic cell death. Matrix-degrading metalloproteinases (MMPs) are neutral proteases involved in extracellular matrix damage. Type IV collagenase is an MMP that increases cerebral capillary permeability after intracerebral injection and may be important along with plasminogen activators (PA) in secondary brain edema in stroke. Therefore, we measured MMPs and PAs in spontaneously hypertensive (SHR) or Wistar-Kyoto (WKY) rats with permanent middle cerebral artery occlusion (MCAO). Brain tissue was assayed for MMPs and PAs at 1, 3, 12, and 24 h and 5 days after occlusion, using substrate gel Polyacrylamide electrophoresis (zymography). SHR showed an increase in 92-kDa type IV collagenase (gelatinase B) in the infarcted hemisphere compared with the opposite side at 12 and 24 h ( p < 0.05). Gelatinase A remained the same in both infarcted and normal tissue until 5 days after injury, when it increased significantly ( p < 0.05). Urokinase-type PA was increased significantly at 12 and 24 h and 5 days, while tissue-type PA was decreased significantly at 1, 12, and 24 h in the ischemic compared with the nonischemic hemisphere. Gelatinase B was markedly increased in SHR at 12 and 24 h compared with WKY ( p < 0.05). Secondary vasogenic edema is maximal 1–2 days after a stroke, which is the time that gelatinase B was elevated. The time of appearance of gelatinase B suggests a role in secondary tissue damage and vasogenic edema, while gelatinase A may be involved in tissue repair.

scholarly journals Cell-mediated degradation of type IV collagen and gelatin films is dependent on the activation of matrix metalloproteinases

1992 ◽  
Vol 288 (2) ◽  
pp. 605-611 ◽  
Author(s):  
S J Atkinson ◽  
R V Ward ◽  
J J Reynolds ◽  
G Murphy
Keyword(s):  
Matrix Metalloproteinases ◽  
Oxygen Radicals ◽  
Type Iv Collagen ◽  
Model System ◽  
Dermal Fibroblasts ◽  
Gelatinase A ◽  
Reactive Oxygen Metabolite ◽  
Gelatinase B ◽  
Type Iv ◽  
Gelatin Films

The ability of normal rabbit dermal fibroblasts to degrade films of type IV collagen and gelatin when stimulated by phorbol ester was shown to be dependent on the induction, secretion and activation of 95 kDa gelatinase B and the secretion and activation of 72 kDa gelatinase A and stromelysin. Degradation was inhibited by exogenous human recombinant tissue inhibitor of metalloproteinases-1, specific antibodies to gelatinase and stromelysin and by the reactive-oxygen-metabolite inhibitor catalase. We discuss the various pathways for activation of matrix metalloproteinases in this model system and conclude that, although plasmin may play a key role in the activation of gelatinase B and stromelysin, gelatinase A is activated by a mechanism which has yet to be elucidated. The involvement of oxygen radicals in the direct activation of matrix metalloproteinases in this model is thought to be unlikely.

Glucose-induced changes in integrins and matrix-related functions in cultured human glomerular epithelial cells

2003 ◽  
Vol 284 (4) ◽  
pp. F671-F679 ◽  
Author(s):  
Paraskevi V. Kitsiou ◽  
Athina K. Tzinia ◽  
William G. Stetler-Stevenson ◽  
Alfred F. Michael ◽  
Wei-Wei Fan ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
High Glucose ◽  
Type Iv Collagen ◽  
Specific Inhibitor ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Matrix Metalloproteinase 2 ◽  
Cell Binding ◽  
Type Iv ◽  
Glomerular Epithelial Cells ◽  
Basement Membrane Thickening

In cultured human glomerular epithelial cells (HGEC), 25 mM glucose resulted in decreased expression of α3-, α2-, and β1-integrins and increased expression of α5- and αvβ3-integrins. This change was accompanied by decreased binding of HGEC to type IV collagen. In the presence of normal (5 mM) glucose concentration, cell binding to type IV collagen was primarily mediated by α2β1- and α5β1-integrins, as indicated by experiments in which cell adhesion to type IV collagen was competed by specific anti-integrin monoclonal antibodies. In the presence of high (25 mM) glucose, the upregulated α5- and αvβ3-integrins were mainly involved in cell binding to type IV collagen. Furthermore, high glucose decreased expression of matrix metalloproteinase-2 (MMP-2), a collagenase regulated in part by α3β1-integrin, as suggested by the use of ligand-mimicking antibodies against these integrins, which resulted in release of increased amounts of MMP-2 in the culture medium. Finally, tissue inhibitor of metalloproteinase-2, the specific inhibitor of MMP-2, was upregulated in high glucose and could contribute to matrix accumulation. These changes could help explain basement membrane thickening in diabetes.

scholarly journals Interferon-γ inhibits sirtuin 6 gene expression in intestinal epithelial cells through a microRNA-92b-dependent mechanism

2020 ◽  
Vol 318 (4) ◽  
pp. C732-C739
Author(s):  
Fangyi Liu ◽  
Xiao Wang ◽  
Hua Geng ◽  
Heng-Fu Bu ◽  
Peng Wang ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Protein Expression ◽  
Intestinal Epithelial Cells ◽  
Specific Inhibitor ◽  
In Silico Analysis ◽  
Interferon Γ ◽  
Luciferase Assay ◽  
Epithelial Cell Line ◽  
Dependent Manner ◽  
Intestinal Epithelial

Sirtuin 6 (Sirt6) is predominantly expressed in epithelial cells in intestinal crypts. It plays an important role in protecting intestinal epithelial cells against inflammatory injury. Previously, we found that colitis is associated with the downregulation of Sirt6 protein in the intestines. Here, we report that murine interferon-γ (Ifnγ) inhibits Sirt6 protein but not mRNA expression in young adult mouse colonocytes (YAMC, a mouse colonic epithelial cell line) in a dose- and time-dependent manner. Using microRNA array analysis, we showed that Ifnγ induces expression of miR-92b in YAMC cells. With in silico analysis, we found that the Sirt6 3′-untranslated region (UTR) contains a putative binding site for miR-92b. Luciferase assay showed that Ifnγ inhibited Sirt6 3′-UTR activity and this effect was mimicked by miR-92b via directly targeting the miR-92b seed site in the 3′-UTR of Sirt6 mRNA. Furthermore, Western blot demonstrated that miR-92b downregulated Sirt6 protein expression in YAMC cells. Blocking miR-92b with a specific inhibitor attenuated the inhibitory effect of Ifnγ on Sirt6 protein expression in the cells. Collectively, our data suggest that Ifnγ inhibits Sirt6 protein expression in intestinal epithelial cells via a miR-92b-mediated mechanism. miR-92b may be a novel therapeutic target for rescuing Sirt6 protein levels in intestinal epithelial cells, thereby protecting against intestinal mucosal injury caused by inflammation.

930 HELICOBACTER PYLORI PROMOTES THE DIFFERENTIATION OF PPAR∂-EXPRESSING EPITHELIAL CELLS FROM LRIG+ STEM CELLS IN A CAG TYPE IV SECRETION SYSTEM-DEPENDENT MANNER

2020 ◽  
Vol 158 (6) ◽  
pp. S-185
Author(s):  
Lydia Wroblewski ◽  
Alberto Delgado ◽  
Maria B. Piazuelo ◽  
Judith Romero-Gallo ◽  
Robert J. Coffey ◽  
...  
Keyword(s):  
Stem Cells ◽  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Secretion System ◽  
Type Iv Secretion ◽  
Type Iv Secretion System ◽  
Dependent Manner ◽  
Type Iv

scholarly journals Regulation of Type IV Collagen α Chains of Glomerular Epithelial Cells in Diabetic Conditions

2009 ◽  
Vol 24 (5) ◽  
pp. 837 ◽  
Author(s):  
Tae-Sun Ha ◽  
Eun-Jeong Hong ◽  
Eun-Mi Ahn ◽  
Hee-Yul Ahn
Keyword(s):  
Epithelial Cells ◽  
Type Iv Collagen ◽  
Type Iv ◽  
Glomerular Epithelial Cells
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