Metal-Catalyzed Oxidation of Extracellular Matrix Proteins Promotes Human Mesangial Cell Apoptosis and Is Associated with Enhanced Expression of Bax and Caspase Activation

2002 ◽  
Vol 292 (3) ◽  
pp. 652-658 ◽  
Author(s):  
Joseph Mattana ◽  
Sergei Kochlatyi ◽  
Nora Gibbons
Keyword(s):  
Extracellular Matrix ◽  
Cell Apoptosis ◽  
Mesangial Cell ◽  
Extracellular Matrix Proteins ◽  
Matrix Proteins ◽  
Caspase Activation ◽  
Enhanced Expression ◽  
Metal Catalyzed Oxidation ◽  
Metal Catalyzed ◽  
Catalyzed Oxidation

scholarly journals Kidney glycosphingolipids are elevated early in diabetic nephropathy and mediate hypertrophy of mesangial cells

2015 ◽  
Vol 309 (3) ◽  
pp. F204-F215 ◽  
Author(s):  
Marimuthu Subathra ◽  
Midhun Korrapati ◽  
Lauren A. Howell ◽  
John M. Arthur ◽  
James A. Shayman ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Diabetic Nephropathy ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Extracellular Matrix Proteins ◽  
Matrix Proteins ◽  
Limited Attention ◽  
Glomerular Hypertrophy ◽  
Glucosylceramide Synthase ◽  
Cell Hypertrophy

Glycosphingolipids (GSLs) play a role in insulin resistance and diabetes, but their role in diabetic nephropathy (DN) has received limited attention. We used 9- and 17-wk-old nondiabetic db/ m and diabetic db/ db mice to examine the role of GSLs in DN. Cerebrosides or monoglycosylated GSLs [hexosylceramides (HexCers); glucosyl- and galactosylceramides] and lactosylceramide (LacCers) were elevated in db/ db mouse kidney cortices, specifically in glomeruli, and also in urine. In our recent paper (25), we observed that the kidneys exhibited glomerular hypertrophy and proximal tubular vacuolization and increased fibrosis markers at these time points. Mesangial cells contribute to hyperglycemia-induced glomerular hypertrophy in DN. Hyperglycemic culture conditions, similar to that present in diabetes, were sufficient to elevate mesangial cell HexCers and increase markers of fibrosis, extracellular matrix proteins, and cellular hypertrophy. Inhibition of glucosylceramide synthase or lowering glucose levels decreased markers of fibrosis and extracellular matrix proteins and reversed mesangial cell hypertrophy. Hyperglycemia increased phosphorylated (p)SMAD3 and pAkt levels and reduced phosphatase and tensin homolog levels, which were reversed with glucosylceramide synthase inhibition. These data suggest that inhibition of glucosylceramide synthase reversed mesangial cell hypertrophy through decreased pAkt and pSmad3 and increased pathways responsible for protein degradation. Importantly, urinary GSL levels were higher in patients with DN compared with healthy control subjects, implicating a role for these lipids in human DN. Thus, hyperglycemia in type II diabetes leads to renal dysfunction at least in part by inducing accumulation of HexCers and LacCers in mesangial cells, resulting in fibrosis, extracellular matrix production, and hypertrophy.

Glomerular mesangial cell adhesion to fibrinogen is mediated by αvβ3 integrin

2004 ◽  
Vol 82 (5) ◽  
pp. 597-601 ◽  
Author(s):  
Edgar G Fischer
Keyword(s):  
Extracellular Matrix ◽  
Cell Adhesion ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Extracellular Matrix Proteins ◽  
Matrix Proteins ◽  
Biological Behavior ◽  
Αvβ3 Integrin ◽  
Glomerular Mesangial Cells ◽  
Mesangioproliferative Glomerulonephritis

The biological behavior of glomerular mesangial cells is thought to play a critical role in human and experimental forms of mesangioproliferative glomerulonephritis. In these diseases, mesangial cells proliferate and produce increased amounts of extracellular matrix proteins, which can lead to glomerulosclerosis and end-stage renal disease. Mesangial cells interact with extracellular matrix proteins through integrin-mediated cell adhesion. Fibrinogen as a plasma-derived protein is known to be deposited in the mesangium of kidneys affected by mesangioproliferative glomerulonephritis. The adhesive interactions between fibrinogen and mesangial cells, however, have not been reported. Results in this work show that mesangial cells adhere to immobilized fibrinogen in an integrin-dependent fashion. This process was inhibited by the αvβ3-selective peptide cyclo-RGDFV and the monoclonal anti-β3 integrin chain antibody F11. Ca2+ ions are a known strong inhibitor of the fibrinogen-αvβ3 interaction, and mesangial cell adhesion did not occur when Ca2+ was the only divalent cation present. Therefore, mesangial cell adhesion to fibrinogen is mediated by αvβ3 integrin, and divalent cations have a fundamental role in regulating this process.Key words: glomerular mesangial cells, adhesion, extracellular matrix, fibrinogen, integrins, αvβ3.

scholarly journals Metal-catalyzed oxidation of extracellular matrix increases macrophage nitric oxide generation

1998 ◽  
Vol 54 (5) ◽  
pp. 1581-1592 ◽  
Author(s):  
Joseph Mattana ◽  
Linda Margiloff ◽  
Larissa Chaplia ◽  
Andrew Chow ◽  
Pravin C. Singhal
Keyword(s):  
Nitric Oxide ◽  
Extracellular Matrix ◽  
Metal Catalyzed Oxidation ◽  
Metal Catalyzed ◽  
Catalyzed Oxidation

Extracellular matrix proteins control the growth of cerebellar medulloblastoma cells

2004 ◽  
Vol 216 (03) ◽  
Author(s):  
U Schüller ◽  
W Hartmann ◽  
A Koch ◽  
K Schilling ◽  
OD Wiestler ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Extracellular Matrix Proteins ◽  
Matrix Proteins ◽  
Cerebellar Medulloblastoma
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