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

Abstract. Endothelin-1 (ET-1) has been implicated in the pathogenesis of renal inflammation. This study investigated the mechanisms underlying the synergistic upregulation of preproET-1 gene expression in human mesangial cells after co-stimulation with thrombin and tumor necrosis factor α (TNFα). Whereas thrombin induced a moderate upregulation of preproET-1 mRNA, co-stimulation with TNFα resulted in a strong and protracted upregulation of this mRNA species. Thrombin+TNFα-induced upregulation of preproET-1 expression was found to require p38 mitogen-activated protein kinase and protein kinases C, whereas activation of extracellular signal-regulated kinase, c-Jun-N-terminal kinase, or intracellular Ca2+ release were not required. Actinomycin D chase experiments suggested that enhanced stability of preproET-1 mRNA did not account for the increase in transcript levels. PreproET-1 promoter analysis demonstrated that the 5′-flanking region of preproET-1 encompassed positive regulatory elements engaged by thrombin. Negative modulation of thrombin-induced activation exerted by the distal 5′ portion of preproET-1 promoter (-4.4 kbp to 204 bp) was overcome by co-stimulation with TNFα, providing a possible mechanism underlying the synergistic upregulation of preproET-1 expression by these two agonists. In conclusion, human mesangial cell expression of preproET-1 may be increased potently in the presence of two common proinflammatory mediators, thereby providing a potential mechanism for ET-1 production in inflammatory renal disease.

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Mechanical stretch-induced fibronectin and transforming growth factor-beta1 production in human mesangial cells is p38 mitogen-activated protein kinase-dependent

Diabetes ◽

10.2337/diabetes.49.4.655 ◽

2000 ◽

Vol 49 (4) ◽

pp. 655-661 ◽

Cited By ~ 84

Author(s):

G. Gruden ◽

S. Zonca ◽

A. Hayward ◽

S. Thomas ◽

S. Maestrini ◽

...

Keyword(s):

Growth Factor ◽

Protein Kinase ◽

Transforming Growth Factor ◽

Mesangial Cells ◽

Mechanical Stretch ◽

Mitogen Activated Protein Kinase ◽

Transforming Growth Factor Beta1 ◽

Human Mesangial Cells ◽

Mitogen Activated Protein

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Norcantharidin Enhances High Concentrations of Fetal Bovine Serum-Induced Apoptosis in Human Mesangial Cells by Regulating the Mitogen-Activated Protein Kinase Signaling Pathway

Kidney & Blood Pressure Research ◽

10.1159/000502524 ◽

2019 ◽

Vol 44 (6) ◽

pp. 1339-1351

Author(s):

Kun Ye ◽

Qiao-Yu Wei ◽

Teng-Xiang Long ◽

Hong-Guang He ◽

Yun-Feng Huang ◽

...

Keyword(s):

Protein Kinase ◽

Bovine Serum ◽

Mesangial Cells ◽

Fetal Bovine Serum ◽

Mitogen Activated Protein Kinase ◽

Human Mesangial Cells ◽

Mitogen Activated Protein ◽

Fetal Bovine ◽

Protein Kinase Signaling

Aim: This study aimed to investigate the effect of norcantharidin (NCTD) on human mesangial cells (HMCs) apoptosis in vitro and further examine its molecular mechanism. Methods: HMCs were divided into 5 groups: control group, 25% fetal bovine serum (FBS)-treated group, and NCTD groups (NCTD [2.5, 5 and 10 µg/mL] + 25% FBS, respectively). Cell proliferation was determined by MTT assay, while apoptosis was evaluated by Hoechest 33258 staining, the level of cytochrome c, immunohistochemistry, and apoptotic-related proteins/gene expression. Results: Cell viability was inhibited in NCTD-treated HMCs in a dose-dependent manner. The number of apoptotic cells and the content of cytochrome c were significantly increased by NCTD treatment but that of mitochondrial membrane was decreased. Moreover, the expression of bcl-2 and caspase-3 was prompted by NCTD, but the expression of bax, MMP-2, and MMP-9 in 25% FBS-treated HMCs was inhibited. In addition, NCTD markedly unregulated the expression of apoptosis-related gene/protein, including p-Erk1/2, phosphorylated-Jun N-terminal kinase (JNK), p-p38, and p53. Conclusion: NCTD enhances 25% FBS-treated HMC apoptosis in vitro, and this effect may be attributed to the modulation of the ERK, JNK, and p38 mitogen-activated protein kinase signaling pathways.

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

Journal of the American Society of Nephrology ◽

10.1681/asn.v1191607 ◽

2000 ◽

Vol 11 (9) ◽

pp. 1607-1619 ◽

Cited By ~ 1

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.

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