SYMPOSIUM: Experimental Biology 1995 Role of Mesangial Cell Ion Transport in Glomerular Physiology and Disease: PHYSIOLOGICAL ROLE OF LARGE, Ca2+-ACTIVATED K+ CHANNELS 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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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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Perilla frutescens Sprout Extract Protect Renal Mesangial Cell Dysfunction against High Glucose by Modulating AMPK and NADPH Oxidase Signaling

Nutrients ◽

10.3390/nu11020356 ◽

2019 ◽

Vol 11 (2) ◽

pp. 356 ◽

Cited By ~ 5

Author(s):

Ha-Rim Kim ◽

Seon-Young Kim

Keyword(s):

High Glucose ◽

Mesangial Cell ◽

Mesangial Cells ◽

Cell Damage ◽

Perilla Frutescens ◽

Activation Mechanism ◽

Glomerular Mesangial Cells ◽

Ampk Activation ◽

Cell Dysfunction

Perilla frutescens (L.) Britt. var. japonica (Hassk.) Hara (PF), is a medical herb of the Lamiaceae family. We have previously reported that the PF sprout extract (PFSE) is effective in treating hyperglycemia. However, the role of PFSE on glomerular mesangial cells (MCs) proliferation and the extracellular matrix (ECM) accumulation in a diabetic condition are still unclear. Therefore, in this study, we have investigated the role of PFSE on cell proliferation and ECM accumulation in murine glomerular MCs (MMCs), cultured under a high glucose (HG) condition. PFSE treatment attenuated HG-induced MMCs proliferation and hypertrophy. Moreover, the HG-induced ECM protein, collagen IV and fibronectin, overexpression was abolished by the PFFSE treatment. In addition, PFSE inhibited reactive oxygen species (ROS) overproduction and NOX2 and NOX4 expression in MMCs under a HG condition. Our data further revealed the involvement of mesangial cell damage in AMP-activated kinase (AMPK) activation. PFSE strongly activated AMPK in MMCs under hyperglycemic conditions. These results suggest that PFSE inhibits HG-medicated MC fibrosis through suppressing the activation of NOX2/4 and the AMPK activation mechanism. PFSE may be useful for the prevention or treatment of diabetic nephropathy.

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Endothelium-derived relaxing factor, nitric oxide: effects on and production by mesangial cells and the glomerulus.

Journal of the American Society of Nephrology ◽

10.1681/asn.v381435 ◽

1993 ◽

Vol 3 (8) ◽

pp. 1435-1441

Author(s):

L Raij ◽

P J Shultz

Keyword(s):

Nitric Oxide ◽

Vascular Tone ◽

Mesangial Cell ◽

Mesangial Cells ◽

Glomerular Mesangial Cells ◽

Relaxing Factor ◽

Endothelium Derived Relaxing Factor

The endothelium-derived relaxing factor nitric oxide (EDRF/NO) is a labile, endogenous vasodilator that is important in the control of systemic vascular tone. This review focuses on the effects of EDRF/NO on glomerular mesangial cells in vitro and on the role of EDRF/NO in mesangial and glomerular physiology and pathophysiology in vivo. It was concluded that EDRF/NO can stimulate increases in cGMP, inhibit mesangial cell contraction, and inhibit growth factor-induced proliferation of mesangial cells in culture. Furthermore, incubation with endotoxin or cytokines stimulates mesangial cells to produce EDRF/NO, via an inducible NO synthase enzyme. Therefore, it is likely that NO could play a role in the inflammatory response within the glomerulus. Finally, recent studies providing evidence that EDRF/NO is functional within the glomerulus in vivo, especially during endotoxemia and inflammation are also reviewed.

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