TNF-Alpha and IL-1Beta-Mediated Regulation of MMP-9 and TIMP-1 in Human Glomerular Mesangial Cells

2007 ◽  
Vol 107 (2) ◽  
pp. e73-e86 ◽  
Author(s):  
Larine Nee ◽  
Niamh Tuite ◽  
Michael P. Ryan ◽  
Tara McMorrow
Keyword(s):  
Mesangial Cells ◽  
Tnf Alpha ◽  
Glomerular Mesangial Cells ◽  
Human Glomerular Mesangial Cells

scholarly journals Tumor necrosis factor alpha activates soluble guanylate cyclase in bovine glomerular mesangial cells via an L-arginine-dependent mechanism.

1990 ◽  
Vol 172 (6) ◽  
pp. 1843-1852 ◽  
Author(s):  
P A Marsden ◽  
B J Ballermann
Keyword(s):  
Guanylate Cyclase ◽  
Mesangial Cell ◽  
Soluble Guanylate Cyclase ◽  
Mesangial Cells ◽  
Tnf Alpha ◽  
Dependent Manner ◽  
Glomerular Mesangial Cells ◽  
Concentration Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Factor Alpha

Endothelium-derived nitric oxide (NO) causes vasodilatation by activating soluble guanylate cyclase, and glomerular mesangial cells respond to NO with elevations of intracellular guanosine 3',5'-cyclic monophosphate (cGMP). We explored whether mesangial cells can be stimulated to produce NO and whether NO modulates mesangial cell function in an autocrine or paracrine fashion. Tumor necrosis factor alpha (TNF-alpha) raised mesangial cell cGMP levels in a time- and concentration-dependent manner (threshold dose 1 ng/ml, IC50 13.8 ng/ml, maximal response 100 ng/ml). TNF-alpha-induced increases in mesangial cGMP content were evident at 8 h and maximal at 18-24 h. The TNF-alpha-induced stimulation of mesangial cell cGMP production was abrogated by actinomycin D or cycloheximide suggesting dependence on new RNA or protein synthesis. Hemoglobin and methylene blue, both known to inhibit NO action, dramatically reduced TNF-alpha-induced mesangial cell cGMP production. Superoxide dismutase, known to potentiate NO action, augmented the TNF-alpha-induced effect. Ng-monomethyl-L-arginine (L-NMMA) decreased cGMP levels in TNF-alpha-treated, but not vehicle-treated mesangial cells in a concentration-dependent manner (IC50 53 microM). L-arginine had no effect on cGMP levels in control or TNF-alpha-treated mesangial cells but reversed L-NMMA-induced inhibition. Interleukin 1 beta and lipopolysaccharide (LPS), but not interferon gamma, also increased mesangial cell cGMP content. Transforming growth factor beta 1 blunted the mesangial cell response to TNF-alpha. TNF-alpha-induced L-arginine-dependent increases in cGMP were also evident in bovine renal artery vascular smooth muscle cells, COS-1 cells, and 1502 human fibroblasts. These findings suggest that TNF-alpha induces expression in mesangial cell of an enzyme(s) involved in the formation of L-arginine-derived NO. Moreover, the data indicate that NO acts in an autocrine and paracrine fashion to activate mesangial cell soluble guanylate cyclase. Cytokine-induced formation of NO in mesangial and vascular smooth muscle cells may be implicated in the pathogenesis of septic shock.

Human glomerular mesangial cells inactivate leukotriene B4 by reduction into dihydro-leukotriene B4 metabolites

Life Sciences ◽  
1990 ◽  
Vol 46 (20) ◽  
pp. 1465-1470 ◽  
Author(s):  
V. Kaever ◽  
J. Bruuns ◽  
J. Wunder ◽  
B. Damerau ◽  
G. Zimmer ◽  
...  
Keyword(s):  
Mesangial Cells ◽  
Leukotriene B4 ◽  
Glomerular Mesangial Cells ◽  
Human Glomerular Mesangial Cells

Mitogenic signaling of thrombin in mesangial cells: role of tyrosine phosphorylation

1994 ◽  
Vol 267 (4) ◽  
pp. F528-F536 ◽  
Author(s):  
G. Grandaliano ◽  
G. G. Choudhury ◽  
P. Biswas ◽  
H. E. Abboud
Keyword(s):  
Gene Expression ◽  
Dna Synthesis ◽  
Tyrosine Phosphorylation ◽  
Mesangial Cells ◽  
Cellular Proteins ◽  
Chain Gene ◽  
Protein Tyrosine Phosphorylation ◽  
Glomerular Mesangial Cells ◽  
Human Glomerular Mesangial Cells

Thrombin elicits multiple biological effects on a variety of cells. We have previously shown that thrombin is a potent mitogen for human glomerular mesangial cells. This mitogenic effect of thrombin is associated with activation of phospholipase C (PLC) and induction of platelet-derived growth factor (PDGF) gene expression. The thrombin receptor, which belongs to the guanine nucleotide binding protein (G protein)-coupled receptor family, has recently been shown to induce rapid tyrosine phosphorylation of cellular proteins. In the present study, we investigated the role of protein-tyrosine phosphorylation in mediating the cellular responses elicited by thrombin in human glomerular mesangial cells. Amino acid labeling followed by immunoprecipitation with phosphotyrosine antibodies demonstrate that thrombin stimulates tyrosine phosphorylation of a set of cellular proteins. Treatment of mesangial cells with thrombin followed by immunoblotting with phosphotyrosine antibodies showed three major bands of tyrosine-phosphorylated proteins approximately 130, 70, and 44-42 kDa. Phosphorylation of these proteins was inhibited by two tyrosine kinase inhibitors, herbimycin A and genistein. Both compounds inhibited DNA synthesis and PDGF B-chain gene expression but had no effect on inositol phosphates production or increases in cytosolic calcium in response to thrombin. These data demonstrate that protein-tyrosine phosphorylation is not required for thrombin-induced PLC activation with inositol phosphate formation and subsequent intracellular calcium release, but it is an absolute requirement for thrombin-induced DNA synthesis and PDGF B-chain gene expression.

Mesangial cells express PDGF mRNAs and proliferate in response to PDGF

1988 ◽  
Vol 255 (4) ◽  
pp. F674-F684 ◽  
Author(s):  
P. J. Shultz ◽  
P. E. DiCorleto ◽  
B. J. Silver ◽  
H. E. Abboud
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Northern Blot Analysis ◽  
Mesangial Cells ◽  
Glomerular Mesangial Cells ◽  
Human Mesangial Cells ◽  
Human Foreskin Fibroblasts ◽  
Human Glomerular Mesangial Cells ◽  
Paracrine Growth Factor

Platelet-derived growth factor (PDGF) is a potent mitogen for cells of mesenchymal origin and is released and/or synthesized by platelets, macrophages, endothelial cells, and rat mesangial cells. In the present investigation, we found that human glomerular mesangial cells in culture release a PDGF-like protein which competes for 125I-PDGF binding to human foreskin fibroblasts and is mitogenic for these fibroblasts. The competing and to a lesser extent the mitogenic activities present in the conditioned medium are partially recognized by an anti-PDGF antibody. Northern blot analysis of poly(A)+ RNA from human mesangial cells demonstrates the expression of both PDGF A- and B-chain mRNAs. PDGF also binds to mesangial cells in a specific manner and stimulates DNA synthesis and cell proliferation. These data suggest that a PDGF-like protein secreted by mesangial cells or released from platelets, monocytes, or endothelial cells during glomerular inflammation may function as an autocrine or a paracrine growth factor for these cells. The biological role of PDGF in mediating proliferative and other inflammatory events in the glomerulus remains to be identified.

scholarly journals Catecholamines Block the Antimitogenic Effect of Estradiol on Human Glomerular Mesangial Cells

Hypertension ◽  
2003 ◽  
Vol 42 (3) ◽  
pp. 349-355 ◽  
Author(s):  
Raghvendra K. Dubey ◽  
Lefteris C. Zacharia ◽  
Delbert G. Gillespie ◽  
Bruno Imthurn ◽  
Edwin K. Jackson
Keyword(s):  
Mesangial Cells ◽  
Glomerular Mesangial Cells ◽  
Human Glomerular Mesangial Cells

Losartan inhibits STAT1 activation and protects human glomerular mesangial cells from angiotensin II induced premature senescence

2012 ◽  
Vol 90 (1) ◽  
pp. 89-98 ◽  
Author(s):  
Sumin Jiao ◽  
Xiaoyu Zheng ◽  
Xue Yang ◽  
Jin Zhang ◽  
Lining Wang
Keyword(s):  
Angiotensin Ii ◽  
Mesangial Cells ◽  
Morphological Changes ◽  
Positive Staining ◽  
Ang Ii ◽  
Glomerular Mesangial Cells ◽  
Cycle Arrest ◽  
Age Related ◽  
Elevated Expression ◽  
Human Glomerular Mesangial Cells

Human glomerular mesangial cells (HMCs) have a finite lifespan, and eventually enter irreversible growth arrest known as cellular senescence, which is thought to contribute to kidney ageing and age-related kidney disorders, such as chronic kidney disease. The signal transducer and activator of transcription 1 (STAT1) is a latent transcription factor involved in a variety of signal transduction pathways, including cell proliferation, apoptosis, and differentiation, but whether it could regulate HMC senescence still remains to be explored. In our study, the induction of angiotensin II (Ang II)-accelerated HMC senescence, as judged by increased senescence-associated β-galactosidase (SA-β-gal)-positive staining cells, morphological changes, and G0/G1 cell cycle arrest. STAT1 activity and the expression of p53 and p21Cip1 were increased after Ang II treatment. STAT1 knockdown using RNA interference significantly inhibited the progression of HMC senescence and decreased the elevated expression of p53 and p21Cip1. Pretreating HMCs with Ang II receptor blocker losartan also inhibited the progression of HMC senescence and STAT1 activity. Our results indicate that STAT1 is implicated in the mediation of Ang II-induced HMC senescence through p53/ p21Cip1 pathway, and that losartan could attenuate HMC senescence by regulating STAT1. The antioxidant N-acetyl-L-cysteine reduced ROS production and STAT1 activity induced by Ang II, indicating that Ang II uses ROS as a second messenger to regulate STAT1 activity.

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