scholarly journals Effects of high glucose on the production of heparan sulfate proteoglycan by mesangial and epithelial cells

1996 ◽  
Vol 49 (4) ◽  
pp. 1079-1089 ◽  
Author(s):  
Nicole F. van Det ◽  
Jacob van den Born ◽  
Jouke T. Tamsma ◽  
Nicole A.M. Verhagen ◽  
Jo H.M. Berden ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Heparan Sulfate ◽  
High Glucose ◽  
Heparan Sulfate Proteoglycan ◽  
Sulfate Proteoglycan

Amphiregulin in lung branching morphogenesis: interaction with heparan sulfate proteoglycan modulates cell proliferation

Development ◽  
1996 ◽  
Vol 122 (6) ◽  
pp. 1759-1767 ◽  
Author(s):  
L. Schuger ◽  
G.R. Johnson ◽  
K. Gilbride ◽  
G.D. Plowman ◽  
R. Mandel
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cells ◽  
Heparan Sulfate ◽  
Branching Morphogenesis ◽  
Mesenchymal Cells ◽  
Heparan Sulfate Proteoglycan ◽  
Sulfate Proteoglycan ◽  
Epithelial Proliferation ◽  
Differential Cell ◽  
Embryonic Lungs

Epithelial and mesenchymal cells isolated from mouse embryonic lungs synthesized and responded to amphiregulin (AR) in a different fashion. Mesenchymal cells produced and deposited 3- to 4-fold more AR than epithelial cells, proliferated in the presence of exogenous AR, and their spontaneous growth was blocked by up to 85% by anti-AR antibodies. In contrast, epithelial cells exhibited a broad response to this growth regulator factor depending on whether they were supplemented with extracellular matrix (ECM) and whether this ECM was of epithelial or mesenchymal origin. AR-treated epithelial cells proliferated by up to 3-fold in the presence of mesenchymal-deposited ECM, remained unchanged in the presence of epithelial-deposited ECM, and decreased in their proliferation rate below controls in the absence of ECM supplementation. This effect was abolished by treatment with the glycosaminoglycan-degrading enzymes heparinase and heparitinase suggesting the specific involvement of heparan sulfate proteoglycan (HSPG) in AR-mediated cell proliferation. In whole lung explants, branching morphogenesis was inhibited by antibodies against the AR heparan sulfate binding site and stimulated by exogenous AR. Since during development, epithelial cells are in contact with mesenchymal ECM at the tips of the growing buds and alongside the basement membrane, focal variations in the proportion of epithelial and mesenchymal HSPG will focally affect epithelial proliferation rates. Therefore, AR-HSPG interaction may underlie the process of branching morphogenesis by inducing differential cell proliferation.

High glucose-induced TGF-beta 1 regulates mesangial production of heparan sulfate proteoglycan

1996 ◽  
Vol 270 (5) ◽  
pp. F812-F821 ◽  
Author(s):  
V. Kolm ◽  
U. Sauer ◽  
B. Olgemooller ◽  
E. D. Schleicher
Keyword(s):  
Heparan Sulfate ◽  
High Glucose ◽  
Mesangial Cells ◽  
Heparan Sulfate Proteoglycan ◽  
Mrna Levels ◽  
Sulfate Proteoglycan ◽  
Tgf Beta ◽  
Mesangial Proliferation ◽  
Matrix Production ◽  
Dose Dependent

Previous investigations have demonstrated that growing mesangial cells in high glucose concentration stimulates extracellular matrix synthesis and also increases the expression of transforming growth factor-beta (TGF-beta). We examined the effects of hyperglycemia on mesangial proliferation and heparan sulfate proteoglycan (HSPG) and fibronectin production. Prolonged exposure of mesangial cells to increasing glucose concentrations resulted in dose-dependent effects on growth inhibition and stimulation of matrix production. Treatment of mesangial cells with high glucose-conditioned medium or with TGF-beta 1 mimicked the effects of high-glucose incubation. Furthermore, TGF-beta 1 caused a dose-dependent increase in HSPG mRNA levels. The high-glucose effects on mesangial cells were preceded by an increase in total TGF-beta 1 protein. The presence of TGF-beta 1 antisense oligonucleotide attenuated the glucose-mediated effects on mesangial proliferation and matrix production. The data show that even moderately elevated glucose concentrations appear to affect the mesangial cells. The results indicate that 1) TGF-beta 1 protein production is necessary to obtain the high glucose-induced effects and 2) TGF-beta 1 stimulates mesangial HSPG expression and production. Because these effects may be attenuated by oligonucleotides antisense to TGF-beta 1, the results suggest a possible way for effective intervention in TGF-beta-mediated glomerulosclerosis.

scholarly journals A heterotrimeric G protein, G alpha i-3, on Golgi membranes regulates the secretion of a heparan sulfate proteoglycan in LLC-PK1 epithelial cells.

1991 ◽  
Vol 114 (6) ◽  
pp. 1113-1124 ◽  
Author(s):  
J L Stow ◽  
J B de Almeida ◽  
N Narula ◽  
E J Holtzman ◽  
L Ercolani ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Heparan Sulfate ◽  
Pertussis Toxin ◽  
Inducible Promoter ◽  
Heparan Sulfate Proteoglycan ◽  
Sulfate Proteoglycan ◽  
Golgi Stack ◽  
Golgi Membranes ◽  
Cytoplasmic Face ◽  
Constitutive Secretion

A heterotrimeric G alpha i subunit, alpha i-3, is localized on Golgi membranes in LLC-PK1 and NRK epithelial cells where it colocalizes with mannosidase II by immunofluorescence. The alpha i-3 was found to be localized on the cytoplasmic face of Golgi cisternae and it was distributed across the whole Golgi stack. The alpha i-3 subunit is found on isolated rat liver Golgi membranes by Western blotting and G alpha i-3 on the Golgi apparatus is ADP ribosylated by pertussis toxin. LLC-PK1 cells were stably transfected with G alpha i-3 on an MT-1, inducible promoter in order to overexpress alpha i-3 on Golgi membranes. The intracellular processing and constitutive secretion of the basement membrane heparan sulfate proteoglycan (HSPG) was measured in LLC-PK1 cells. Overexpression of alpha i-3 on Golgi membranes in transfected cells retarded the secretion of HSPG and accumulated precursors in the medial-trans-Golgi. This effect was reversed by treatment of cells with pertussis toxin which results in ADP-ribosylation and functional uncoupling of G alpha i-3 on Golgi membranes. These results provide evidence for a novel role for the pertussis toxin sensitive G alpha i-3 protein in Golgi trafficking of a constitutively secreted protein in epithelial cells.

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