scholarly journals Renin-stimulated TGF-β1 expression is regulated by a mitogen-activated protein kinase in mesangial cells

2007 ◽  
Vol 72 (1) ◽  
pp. 45-52 ◽  
Author(s):  
Y. Huang ◽  
N.A. Noble ◽  
J. Zhang ◽  
C. Xu ◽  
W.A. Border
Keyword(s):  
Protein Kinase ◽  
Mesangial Cells ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Tgf Β1

scholarly journals The Decorin High Glucose Response Element and Mechanism of Its Activation in Human Mesangial Cells

2000 ◽  
Vol 11 (9) ◽  
pp. 1607-1619 ◽  
Author(s):  
NADIA ABDEL WAHAB ◽  
SUSAN PARKER ◽  
JEAN-DANIEL SRAER ◽  
ROGER M. MASON
Keyword(s):  
Protein Kinase ◽  
High Glucose ◽  
Nuclear Translocation ◽  
Mesangial Cells ◽  
Mitogen Activated Protein Kinase ◽  
Glucose Medium ◽  
Response Element ◽  
Human Mesangial Cells ◽  
Mitogen Activated Protein ◽  
Tgf Β1

Abstract. The decorin gene encodes a proteoglycan with putative structural and regulatory functions whose expression is markedly increased in human mesangial cells (HMC) exposed to high concentrations of glucose (15 to 30 mM). The gene has two promoters (P1 and P2) upstream of two alternative first exons. Transcripts driven by both promoters are present in HMC maintained in 4 mM D-glucose medium. After exposure to 30 mM D-glucose for 7 to 21 d, transcripts driven by P1 are markedly increased, whereas those driven by P2 decrease. Culture in 4 mM D-glucose medium containing transforming growth factor-β1 (TGF-β1) (1.25 ng/ml) has the same effect. However, addition of an excess of TGF-β neutralizing antibody to the 30 mM D-glucose cultures only partly suppressed increased decorin transcription from P1. In transformed HMC transfected with a reporter (p-SAEP) driven by P1 or P2, P1 activity increased twofold on treatment with either 30 mM D-glucose or TGF-β1 in 4 mM medium. P2 had little activity under any conditions. 5′ deletion of P1 showed that basal transcriptional activity lies within the proximal 378 bp, while the major high glucose and TGF-β response element is located in the -683 to -583-bp region. A putative cAMP response-like sequence (TGACGTTT) lies within this region. Electrophoretic mobility shift assays revealed the same pattern of multiple complexes between oligonucleotides containing this sequence and nuclear proteins extracted from HMC maintained in either 4 or 30 mM D-glucose conditions, but the latter were more prominent. cAMP response element binding protein (CREB) was identified as one transcription factor forming these complexes but other factors remain unidentified. Increased levels of phospho-(Ser 133) CREB were found in HMC exposed to 30 mM D-glucose. High glucose also activated and led to nuclear translocation of p42/44 mitogen-activated protein kinase and p38 mitogen-activated protein kinase, both of which can activate CREB by phosphorylation of serine 133.

scholarly journals Applied Pressure Enhances Cell Proliferation through Mitogen-activated Protein Kinase Activation in Mesangial Cells

1998 ◽  
Vol 273 (27) ◽  
pp. 16905-16912 ◽  
Author(s):  
Yasunobu Kawata ◽  
Yoichi Mizukami ◽  
Zenzo Fujii ◽  
Toshihiro Sakumura ◽  
Ken-ichi Yoshida ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Protein Kinase ◽  
Mesangial Cells ◽  
Applied Pressure ◽  
Mitogen Activated Protein Kinase ◽  
Kinase Activation ◽  
Protein Kinase Activation ◽  
Mitogen Activated Protein

Effect of endothelin-1(1-31) on p38 mitogen-activated protein kinase in cultured human mesangial cells

Life Sciences ◽  
2000 ◽  
Vol 68 (6) ◽  
pp. 635-645 ◽  
Author(s):  
Daisuke Inui ◽  
Masanori Yoshizumi ◽  
Yuki Suzaki ◽  
Kazuyoshi Kirima ◽  
Koichiro Tsuchiya ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mesangial Cells ◽  
Mitogen Activated Protein Kinase ◽  
Human Mesangial Cells ◽  
Endothelin 1 ◽  
Mitogen Activated Protein

scholarly journals Lysophosphatidic acid-mediated signal-transduction pathways involved in the induction of the early-response genes prostaglandin G/H synthase-2 and Egr-1: a critical role for the mitogen-activated protein kinase p38 and for Rho proteins

1998 ◽  
Vol 330 (3) ◽  
pp. 1107-1114 ◽  
Author(s):  
O. A. Christian REISER ◽  
Thomas LANZ ◽  
Fred HOFMANN ◽  
Gerhard HOFER ◽  
D. Harald RUPPRECHT ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Lysophosphatidic Acid ◽  
Mesangial Cells ◽  
Early Response ◽  
Mitogen Activated Protein Kinase ◽  
Rho Proteins ◽  
Toxin B ◽  
Mapk Kinase ◽  
Mitogen Activated Protein ◽  
Early Response Genes

During inflammatory processes of the kidney, lesions of the glomerulus lead to aggregation of thrombocytes and infiltration of macrophages, which can release bioactive mediators. One of these important signalling molecules is lysophosphatidic acid (LPA). Incubation of rat mesangial cells with LPA induced mRNA and protein expression of the early-response genes pghs-2 (for prostaglandin G/H synthase-2/cyclo-oxygenase-2) and egr-1. As shown by antisense experiments, induction of egr-1 was related to the strong mitogenic effect of LPA. LPA-mediated gene expression was inhibited by pertussis toxin, indicating coupling to G-proteins of the Gi family. Specific inhibition of proteins of the small G-protein subfamily Rho with toxin B from Clostridium difficile led to changes in mesangial cell morphology without induction of apoptosis. LPA-mediated expression of pghs-2 and egr-1 was reduced to base-line levels by toxin B, indicating a role for Rho proteins in LPA-mediated gene induction. Of the two mitogen-activated protein kinase (MAPK) pathways investigated, the MAPK kinase-extracellular signal-regulated kinase pathway was involved in the induction of both pghs-2 and egr-1 mRNA expression, as shown by the inhibitory effect of PD98059. Activation of the MAPK p38, however, was only related to pghs-2 expression, whereas egr-1 expression was not affected by treatment of mesangial cells with the specific inhibitor SB203580. Taken together our data provide evidence that LPA-mediated activation of MAPK kinase and Rho proteins leads to the induction of the functionally distinct early-response genes pghs-2 and egr-1, whereas activation of MAPK p38 revealed considerable differences between the regulation of these two genes.

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