Increased Effect of Interferon γ on PDGF-Induced c-fos Gene Transcription in Glomerular Mesangial Cells: Differential Effect of the Transcriptional Coactivator CBP on STAT1α Activation

2000 ◽  
Vol 273 (3) ◽  
pp. 1069-1077 ◽  
Author(s):  
Goutam Ghosh Choudhury ◽  
Jill M Ricono
Keyword(s):  
Gene Transcription ◽  
Differential Effect ◽  
Mesangial Cells ◽  
Interferon Γ ◽  
Glomerular Mesangial Cells ◽  
Transcriptional Coactivator

scholarly journals Modulation of IL-6 Expression by KLF4-Mediated Transactivation and PCAF-Mediated Acetylation in Sublytic C5b-9-Induced Rat Glomerular Mesangial Cells

2022 ◽  
Vol 12 ◽  
Author(s):  
Lu Xia ◽  
Yu Liu ◽  
Zhiwei Zhang ◽  
Yajuan Gong ◽  
Tianyi Yu ◽  
...  
Keyword(s):  
Gene Transcription ◽  
Rat Model ◽  
Mesangial Cells ◽  
Histone H3 ◽  
Lysine Residue ◽  
Regulatory Mechanisms ◽  
Glomerular Mesangial Cells ◽  
Mesangial Proliferative Glomerulonephritis ◽  
Histone H2b ◽  
Inflammatory Damage

Interleukin-6 (IL-6) overproduction has been considered to contribute to inflammatory damage of glomerular mesangial cells (GMCs) in human mesangial proliferative glomerulonephritis (MsPGN) and its rat model called Thy-1 nephritis (Thy-1N). However, the regulatory mechanisms of IL-6 expression in GMCs upon sublytic C5b-9 timulation remain poorly understood. We found that Krüppel-like factor 4 (KLF4) bound to the IL-6 promoter (−618 to −126 nt) and activated IL-6 gene transcription. Furthermore, lysine residue 224 of KLF4 was acetylated by p300/CBP-associated factor (PCAF), which was important for KLF4-mediated transactivation. Moreover, lysine residue 5 on histone H2B and lysine residue 9 on histone H3 at the IL-6 promoter were also acetylated by PCAF, which resulted in an increase in IL-6 transcription. Besides, NF-κB activation promoted IL-6 expression by elevating the expression of PCAF. Overall, these findings suggest that sublytic C5b-9-induced the expression of IL-6 involves KLF4-mediated transactivation, PCAF-mediated acetylation of KLF4 and histones, and NF-κB activation in GMCs.

Platelet-activating factor and the kidney

1986 ◽  
Vol 251 (1) ◽  
pp. F1-F11 ◽  
Author(s):  
D. Schlondorff ◽  
R. Neuwirth
Keyword(s):  
De Novo ◽  
Mesangial Cells ◽  
Biological Activities ◽  
Platelet Activating Factor ◽  
Calcium Ionophore ◽  
Initial Step ◽  
Renal Physiology ◽  
Dependent Manner ◽  
Glomerular Mesangial Cells ◽  
Isolated Kidney

Platelet-activating factor (PAF) represents a group of phospholipids with the basic structure of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine. A number of different cells are capable of producing PAF in response to various stimuli. The initial step of PAF formation is activation of phospholipase A2 in a calcium-dependent manner, yielding lyso-PAF. During this step arachidonic acid is also released and can be converted to its respective cyclooxygenase and lipoxygenase products. The lyso-PAF generated is then acetylated in position 2 of the glycerol backbone by a coenzyme A (CoA)-dependent acetyltransferase. An additional pathway may exist whereby PAF is generated de novo from 1-alkyl-2-acetyl-sn-glycerol by phosphocholine transferase. PAF inactivation in cells and blood is by specific acetylhydrolases. PAF exhibits a variety of biological activities including platelet and leukocyte aggregation and activation, increased vascular permeability, respiratory distress, decreased cardiac output, and hypotension. In the kidney PAF can produce decreases in blood flow, glomerular filtration, and fluid and electrolyte excretion. Intrarenal artery injection of PAF may also result in glomerular accumulation of platelets and leukocytes and mild proteinuria. PAF increases prostaglandin formation in the isolated kidney and in cultured glomerular mesangial cells. PAF also causes contraction of mesangial cells. Upon stimulation with calcium ionophore the isolated kidney, isolated glomeruli and medullary cells, and cultured mesangial cells are capable of producing PAF. The potential role for PAF in renal physiology and pathophysiology requires further investigation that may be complicated by 1) the multiple interactions of PAF, prostaglandins, and leukotrienes and 2) the autocoid nature of PAF, which may restrict its action to its site of generation.

scholarly journals Tumour metastasis suppressor, nm23-β, inhibits gelatinase A transcription by interference with transactivator Y-box protein-1 (YB-1)

2002 ◽  
Vol 366 (3) ◽  
pp. 807-816 ◽  
Author(s):  
Sunfa CHENG ◽  
Maria Alexandra ALFONSO-JAUME ◽  
Peter R. MERTENS ◽  
David H. LOVETT
Keyword(s):  
Mesangial Cells ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Repeat Sequence ◽  
Luciferase Reporter ◽  
Metastasis Suppressor ◽  
Gelatinase A ◽  
Glomerular Mesangial Cells ◽  
Tumour Metastasis ◽  
Β Protein

Gelatinase A transcriptional regulation is the consequence of combinatorial interactions with key promoter and enhancer elements identified within this gene. A potent 40bp enhancer response element, RE-1, located in the near 5′ flanking regions of the rat and human gelatinase A genes drives high-level expression in glomerular mesangial cells (MCs). Southwestern-blot analysis of MC nuclear extracts revealed specific interactions of RE-1 with at least four proteins, of which three have been identified as p53, activator protein 2 and the single-stranded DNA-binding factor Y-box protein-1 (YB-1). In the present study, we report the identification of a fourth 17kDa RE-1-binding protein as the rat homologue (nm23-β) of the human nm23-H1 metastasis suppressor gene. Recombinant nm23-β protein bound only the single-stranded forms of the RE-1 sequence. Mutagenesis revealed direct interaction of nm23-β with a repeat sequence, 5′-GGGTTT-3′, shown previously to specifically interact with YB-1 [Mertens, Harendza, Pollock and Lovett (1997) J. Biol. Chem. 272, 22905—22912], and recombinant nm23-β protein competed for single-stranded YB-1 binding. Transient transfection of MC with an nm23-β expression plasmid within the context of a RE-1/simian virus 40 promoter/luciferase reporter yielded a concentration-dependent repression (80—90%) of luciferase activity in MC and Rat1 fibroblasts. A similar pattern of nm23-β repression was demonstrated within the context of the RE-1/homologous gelatinase A promoter. Co-transfection of nm23-β blocked YB-1-mediated activation of transcription and expression of gelatinase A. Nm23-β may be an important physiological regulator of gelatinase A transcription that acts by competitive interference with the single-stranded transactivator YB-1. Gelatinase A is a key mediator of tumour metastasis, suggesting that competitive suppression of transcription by nm23-β (or the human nm23-H1) may be a component of the reduced metastatic capabilities of cells expressing high levels of this protein.

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