Nitric Oxide Modulates the Synthesis of Extracellular Matrix Proteins in Cultured Rat Mesangial Cells

1995 ◽  
Vol 207 (1) ◽  
pp. 120-125 ◽  
Author(s):  
H. Trachtman ◽  
S. Futterweit ◽  
P. Singhal
Keyword(s):  
Nitric Oxide ◽  
Extracellular Matrix ◽  
Mesangial Cells ◽  
Extracellular Matrix Proteins ◽  
Matrix Proteins

Thromboxane stimulates synthesis of extracellular matrix proteins in vitro

1991 ◽  
Vol 261 (3) ◽  
pp. F488-F494 ◽  
Author(s):  
L. A. Bruggeman ◽  
E. A. Horigan ◽  
S. Horikoshi ◽  
P. E. Ray ◽  
P. E. Klotman
Keyword(s):  
Extracellular Matrix ◽  
Matrix Protein ◽  
Mesangial Cells ◽  
Extracellular Matrix Proteins ◽  
Cellular Protein ◽  
Matrix Proteins ◽  
Extracellular Matrix Protein ◽  
Renal Diseases ◽  
Glomerular Mesangial Cells

The vasoconstrictor eicosanoid thromboxane plays an important role in the pathogenesis of several renal diseases. As an autacoid, its local release alters blood flow and induces platelet aggregation. We report a direct stimulatory effect of thromboxane on extracellular matrix protein production and gene expression in vitro. Treatment of two cell types, differentiated mouse teratocarcinoma cells (F9+) and human glomerular mesangial cells, with two different thromboxane analogues resulted in increased production of components of the extracellular matrix including fibronectin and the basement membrane proteins laminin and type IV collagen. These responses to thromboxane were not the result of a mitogenic effect of thromboxane nor the result of an increase in total cellular protein. The increased production of extracellular matrix proteins was, at least in part, due to an increase in the steady-state level of mRNA for these genes. Furthermore, the effect of thromboxane was markedly inhibited by cotreatment with a thromboxane-receptor antagonist. These results suggest a new potential role for thromboxane as a mediator of the sclerotic and fibrotic responses to injury.

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.

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