Lentiviral Vector-Mediated FoxO1 Overexpression Inhibits Extracellular Matrix Protein Secretion Under High Glucose Conditions in Mesangial Cells

2015 ◽  
Vol 117 (1) ◽  
pp. 74-83 ◽  
Author(s):  
Feng Guo ◽  
Qingzhu Wang ◽  
Yingni Zhou ◽  
Lina Wu ◽  
Xiaojun Ma ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Protein Secretion ◽  
High Glucose ◽  
Matrix Protein ◽  
Mesangial Cells ◽  
Lentiviral Vector ◽  
Extracellular Matrix Protein

scholarly journals Glucagon-like peptide-1 receptor pathway inhibits extracellular matrix production by mesangial cells through store-operated Ca2+ channel

2019 ◽  
Vol 244 (14) ◽  
pp. 1193-1201 ◽  
Author(s):  
Linjing Huang ◽  
Rong Ma ◽  
Tingting Lin ◽  
Sarika Chaudhari ◽  
Parisa Y Shotorbani ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
High Glucose ◽  
Protein Production ◽  
Matrix Protein ◽  
Mesangial Cells ◽  
Collagen Iv ◽  
Extracellular Matrix Protein ◽  
Human Mesangial Cells ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glomerular mesangial cell is the major source of mesangial matrix. Our previous study demonstrated that store-operated Ca2+ channel signaling suppressed extracellular matrix protein production by mesangial cells. Recent studies demonstrated that glucagon-like peptide-1 receptor (GLP-1R) pathway had renoprotective effects. However, the underlying mechanism(s) remains unclear. The present study was aimed to determine if activation of GLP-1R decreased extracellular matrix protein production by mesangial cells through upregulation of store-operated Ca2+ function. Experiments were conducted in cultured human mesangial cells. Liraglutide and exendin 9–39 were used to activate and inhibit GLP-1R, respectively. Store-operated Ca2+ function was estimated by evaluating the SOC-mediated Ca2+ entry (SOCE). We found that liraglutide treatment reduced high glucose-stimulated production of fibronectin and collagen IV. The inhibitory effects of liraglutide were not observed in the presence of exendin 9–39. Exendin-4, another GLP-1R agonist also blunted high glucose-stimulated fibronectin and collagen IV production. Treatment of human mesangial cells with liraglutide for 24 h significantly attenuated the high glucose-induced reduction of Orai1 protein. Consistently, Ca2+ imaging experiments showed that the inhibition of high glucose on SOCE was significantly attenuated by liraglutide. However, in the presence of exendin 9–39, liraglutide failed to reverse the high glucose effect. Furthermore, liraglutide effects on fibronectin and collagen IV protein abundance were significantly attenuated by GSK-7975A, a selective blocker of store-operated Ca2+. Taken together, our findings suggest that GLP-1R signaling inhibited high glucose-induced extracellular matrix protein production in mesangial cells by restoring store-operated Ca2+ function. Impact statement Diabetic kidney disease continues to be a major challenge to health care system in the world. There are no known therapies currently available that can cure the disease. The present study provided compelling evidence that activation of GLP-1R inhibited extracellular matrix protein production by glomerular mesangial cells. We further showed that the beneficial effect of GLP-1R was attributed to upregulation of store-operated Ca2+ channel function. Therefore, we identified a novel mechanism contributing to the renal protective effects of GLP-1R pathway. Activation of GLP-1R pathway and/or store-operated Ca2+ channel signaling in MCs could be an option for patients with diabetic kidney disease.

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.

Semiquantitative measurement of total extracellular matrix protein produced by cultured mesangial cells

Nephrology ◽  
1998 ◽  
Vol 4 (5-6) ◽  
pp. 379-383 ◽  
Author(s):  
Tetsuya OOTAKA ◽  
Nobert KRAFT ◽  
Takao SAITO ◽  
Robert C ATKINS
Keyword(s):  
Extracellular Matrix ◽  
Matrix Protein ◽  
Mesangial Cells ◽  
Extracellular Matrix Protein

PPARγ agonists exert antifibrotic effects in renal tubular cells exposed to high glucose

2005 ◽  
Vol 289 (5) ◽  
pp. F1153-F1158 ◽  
Author(s):  
U. Panchapakesan ◽  
S. Sumual ◽  
C. A. Pollock ◽  
X. Chen
Keyword(s):  
Extracellular Matrix ◽  
High Glucose ◽  
Matrix Protein ◽  
Collagen Iv ◽  
Extracellular Matrix Protein ◽  
Total Production ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Nuclear Binding ◽  
Pparγ Agonists

Peroxisome proliferator-activated receptor-γ (PPARγ) are ligand-activated transcription factors that regulate cell growth, inflammation, lipid metabolism, and insulin sensitivity. We recently demonstrated that PPARγ agonists limit high glucose-induced inflammation in a model of proximal tubular cells (PTC; Panchapakesan U, Pollock CA, and Chen XM. Am J Physiol Renal Physiol 287: F528–F534, 2004). However, the role of PPARγ in the excess extracellular matrix production is largely unknown. We evaluated the effect of 24- to 48-h 8 μM l-805645 or 10 μM pioglitazone on 25 mM d-glucose-induced markers of fibrosis in HK-2 cells. High d-glucose induced nuclear binding of activator protein-1 (AP-1) to 140.8 ± 10.9% ( P < 0.05), which was attenuated with L-805645 and pioglitazone to 82.3 ± 14.4 ( P < 0.01 vs. high d-glucose) and 99.3 ± 12.2% ( P < 0.05 vs. high d-glucose), respectively. High d-glucose increased total production of transforming growth factor (TGF)-β1 139.6 ± 6.5% ( P < 0.05), which was reversed with L-805645 and pioglitazone to 68.73 ± 5.7 ( P < 0.01 vs. high d-glucose) and 112 ± 13.6% ( P < 0.05 vs. high d-glucose). L-805645 and pioglitazone reduced high d-glucose-induced fibronectin from 156.0 ± 24.9 ( P < 0.05) to 81.9 ± 16.0 and 57.4 ± 12.7%, respectively (both P < 0.01 vs. high d-glucose). Collagen IV was not induced by high d-glucose. L-805645 and pioglitazone suppressed collagen IV to 68.0 ± 14.5 ( P < 0.05) and 46.5 ± 11.6% ( P < 0.01) vs. high d-glucose, respectively. High d-glucose increased the nuclear binding of NF-κB to 167 ± 22.4% ( P < 0.05), which was not modified with PPARγ agonists. In conclusion, PPARγ agonists exert antifibrotic effects in human PTC in high glucose by attenuating the increase in AP-1, TGF-β1, and the downstream production of the extracellular matrix protein fibronectin.

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