C3 and C4 gene expression and interferon-gamma-mediated regulation in 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.

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Regulation of C3 and factor H synthesis of human glomerular mesangial cells by IL-1 and interferon-gamma

Clinical & Experimental Immunology ◽

10.1111/j.1365-2249.1994.tb06033.x ◽

2008 ◽

Vol 95 (1) ◽

pp. 173-180 ◽

Cited By ~ 45

Author(s):

M. E. A. DOBBELSTEEN ◽

V. VERHASSELT ◽

J. G. J. KAASHOEK ◽

J. J. TIMMERMAN ◽

W. E. M. SCHROEIJERS ◽

...

Keyword(s):

Interferon Gamma ◽

Mesangial Cells ◽

Factor H ◽

Glomerular Mesangial Cells ◽

Human Glomerular Mesangial Cells

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Effect of dopamine on ecto-5′-nucleotidase expression in human glomerular mesangial cells

Archives Internationales de Physiologie de Biochimie et de Biophysique ◽

10.3109/13813459409007533 ◽

1994 ◽

Vol 102 (3) ◽

pp. 171-173 ◽

Cited By ~ 5

Author(s):

P. Vlahovlć ◽

V. Stefanović

Keyword(s):

Mesangial Cells ◽

Glomerular Mesangial Cells ◽

Human Glomerular Mesangial Cells

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MiR-153-3p reduces extracellular matrix accumulation in high glucose-stimulated human glomerular mesangial cells via targeting PAQR3 in diabetic nephropathy

Endocrinología Diabetes y Nutrición ◽

10.1016/j.endinu.2021.03.005 ◽

2021 ◽

Author(s):

Hongli Yang ◽

Xingxing Fang ◽

Yan Shen ◽

Wubin Yao ◽

Dongmei Chen ◽

...

Keyword(s):

Extracellular Matrix ◽

Diabetic Nephropathy ◽

High Glucose ◽

Mesangial Cells ◽

Glomerular Mesangial Cells ◽

Human Glomerular Mesangial Cells ◽

Matrix Accumulation

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

Life Sciences ◽

10.1016/0024-3205(90)90463-2 ◽

1990 ◽

Vol 46 (20) ◽

pp. 1465-1470 ◽

Cited By ~ 15

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

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Pyk2 controls filamentous actin formation in human glomerular mesangial cells via modulation of profilin expression

Cell Health and Cytoskeleton ◽

10.2147/chc.s5667 ◽

2009 ◽

Vol Volume 1 ◽

pp. 17-25

Author(s):

Andrey Sorokin

Keyword(s):

Mesangial Cells ◽

Glomerular Mesangial Cells ◽

Filamentous Actin ◽

Human Glomerular Mesangial Cells

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Mesangial cells express PDGF mRNAs and proliferate in response to PDGF

AJP Renal Physiology ◽

10.1152/ajprenal.1988.255.4.f674 ◽

1988 ◽

Vol 255 (4) ◽

pp. F674-F684 ◽

Cited By ~ 13

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.

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Gene expression profile of endothelin-1-induced growth in glomerular mesangial cells

AJP Cell Physiology ◽

10.1152/ajpcell.00105.2003 ◽

2003 ◽

Vol 285 (5) ◽

pp. C1109-C1115 ◽

Cited By ~ 14

Author(s):

Rangnath Mishra ◽

Patrick Leahy ◽

Michael S. Simonson

Keyword(s):

Gene Expression ◽

Growth Factor ◽

Cell Growth ◽

Gene Expression Profile ◽

Expression Profile ◽

Kinase Inhibitor ◽

Mesangial Cells ◽

Growth Control ◽

Glomerular Mesangial Cells ◽

Regulated Gene Expression

Endothelin (ET)-1 is a vasoconstrictor and mitogen involved in vascular remodeling. Changes in gene expression that underlie control of cell growth by ET-1 remain poorly characterized. To identify pathways of growth control we used microarrays to analyze ET-1-regulated gene expression in human mesangial cells, an important ET-1 vascular target cell in vivo. Statistical assessment of differential expression (significance analysis of microarrays) revealed upregulated transcripts for growth factors [heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), fibroblast growth factor (FGF), interleukin (IL)-6] and downregulated transcripts for genes that inhibit growth (BAX, p27KIP1, DAD1). Consistent with the gene expression profile, quantitative RT-PCR and Western blotting confirmed induction of HB-EGF by ET-1. To test a functional role for HB-EGF in ET-1 signaling, we showed that exogenous HB-EGF stimulated phosphorylation of ErbB1 and growth of mesangial cells. ET-1-induced proliferation was blocked by an ErbB1 receptor-selective kinase inhibitor and by a specific ErbB1 receptor-neutralizing antibody. Proliferation in response to ET-1 was also inhibited by neutralizing antisera against human HB-EGF. Together, these results provide data for modeling ET-1 pathways for growth control and suggest a specific role for HB-EGF gene induction in mesangial cell growth in response to ET-1.

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