scholarly journals Effects of dexamethasone and transforming growth factor-β2 on group II phospholipase A2 mRNA and activity levels in interleukin 1β- and forskolin-stimulated mesangial cells

1996 ◽  
Vol 315 (2) ◽  
pp. 435-441 ◽  
Author(s):  
Margriet J. B. M. VERVOORDELDONK ◽  
Casper G. SCHALKWIJK ◽  
Josef PFEILSCHIFTER ◽  
Henk van den BOSCH
Keyword(s):  
Enzyme Activity ◽  
Growth Factor ◽  
Phospholipase A2 ◽  
Inflammatory Cytokines ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Interleukin 1Β ◽  
Mrna Levels ◽  
Transforming Growth Factor Β2 ◽  
Group Ii

The expression of 14 kDa group II phospholipase A2 [also referred to as secretory PLA2 (sPLA2)] is induced in rat glomerular mesangial cells by exposure to inflammatory cytokines and forskolin, a cAMP elevating agent. Previously we have shown that dexamethasone and transforming growth factor-β2 (TGF-β2) suppress sPLA2 protein synthesis and enzyme activity induced by cytokines and forskolin. The regulation of sPLA2 by pro-inflammatory cytokines suggests that the enzyme may play a role in glomerular inflammatory reactions. In order to understand the regulation of sPLA2 in more detail, we investigated whether dexamethasone and TGF-β2 also suppress sPLA2 mRNA after its induction by either interleukin-1β (IL-1β) or forskolin. We found that IL-1β-induced sPLA2 mRNA in rat mesangial cells is not down-regulated by pretreatment of the cells with dexamethasone, even at a concentration of 10 μM, which dramatically decreases sPLA2 protein levels and activity. Metabolic labelling experiments indicated that the decreased sPLA2 levels under these conditions can be explained by inhibition of the rate of sPLA2 synthesis from the elevated mRNA levels. In contrast, the forskolin-induced elevation of sPLA2 mRNA is inhibited by dexamethasone in a concentration-dependent manner. Likewise, TGF-β2 inhibits the elevation of sPLA2 mRNAs induced by either IL-1β or forskolin. The decrease in sPLA2 mRNA caused by TGF-β2 corresponds with the decrease in sPLA2 enzyme levels and activity. These data suggest that cytokine- and forskolin-induced sPLA2 expression is tightly controlled via both transcriptional and post-transcriptional mechanisms. Furthermore, we show that pretreatment of mesangial cells with epidermal growth factor prior to stimulation with IL-1β or forskolin had no suppressing effect on sPLA2 levels or enzyme activity, as has been reported previously for osteoblasts.

scholarly journals Suppression by cyclosporin A of interleukin 1β -induced expression of group II phospholipase A2 in rat renal mesangial cells

1997 ◽  
Vol 121 (4) ◽  
pp. 787-793 ◽  
Author(s):  
Gaby Walker ◽  
Dieter Kunz ◽  
Werner Pignat ◽  
Henk van den Bosch ◽  
Josef Pfeilschifter
Keyword(s):  
Phospholipase A2 ◽  
Cyclosporin A ◽  
Mesangial Cells ◽  
Interleukin 1Β ◽  
Induced Expression ◽  
Group Ii

scholarly journals Epidermal growth factor and phorbol myristate acetate increase expression of the mRNA for cytosolic phospholipase A2 in glomerular mesangial cells

1993 ◽  
Vol 295 (3) ◽  
pp. 763-766 ◽  
Author(s):  
A P Maxwell ◽  
H J Goldberg ◽  
A H N Tay ◽  
Z G Li ◽  
G S Arbus ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Phospholipase A2 ◽  
Mesangial Cells ◽  
Mrna Levels ◽  
Glomerular Mesangial Cells ◽  
Pla2 Activity ◽  
Mrna Accumulation ◽  
Epidermal Growth

We have previously shown that phospholipase A2 (PLA2) activity is rapidly activated by epidermal growth factor (EGF) and phorbol 12-myristate 13-acetate (PMA) in renal mesangial cells and other cell systems in a manner that suggests a covalent modification of the PLA2 enzyme(s). This PLA2 activity is cytosolic (cPLA2) and is distinct from secretory forms of PLA2, which are also stimulated in mesangial cells in response to cytokines and other agonists. However, longer-term regulation of cPLA2 in renal cells may also occur at the level of gene expression. Cultured rat mesangial cells were used as a model system to test the effects of EGF and PMA on the regulation of cPLA2 gene expression. EGF and PMA both produced sustained increases in cPLA2 mRNA levels, with a parallel increase in enzyme activity over time. Inhibition of protein synthesis by cycloheximide increased basal cPLA2 mRNA accumulation in serum-starved mesangial cells, and the combination of EGF and cycloheximide resulted in super-induction of cPLA2 gene expression compared with EGF alone. Actinomycin D treatment entirely abrogated the effect of EGF on cPLA2 mRNA accumulation. These findings suggest that regulation of cPLA2 is achieved by factors controlling gene transcription and possibly mRNA stability, in addition to previously characterized posttranslational modifications.

Mechanisms through which bradykinin promotes glomerular injury in diabetes

2005 ◽  
Vol 288 (3) ◽  
pp. F483-F492 ◽  
Author(s):  
Yan Tan ◽  
Bing Wang ◽  
Joo-Seob Keum ◽  
Ayad A. Jaffa
Keyword(s):  
Diabetic Nephropathy ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Tissue Growth ◽  
Collagen I ◽  
Mrna Levels ◽  
Glomerular Injury ◽  
Western Blots ◽  
Protein Levels

In diabetes, mesangial cell proliferation and extracellular matrix expansion are critical components in the development of glomerulosclerosis. We reported that diabetes alters the activity of the kallikrein-kinin system and that these alterations contribute to the development of diabetic nephropathy. The present study examined the influence of streptozotocin-induced diabetes on the renal expression of bradykinin (BK) B2 receptors (B2KR), connective tissue growth factor (CTGF), transforming growth factor-β (TGF-β), and TGF-β type II receptor (TGF-βRII) and assessed the signaling mechanisms through which B2KR activation may promote glomerular injury. Eight weeks after the induction of diabetes, renal mRNA levels of B2KR, CTGF, and TGF-β as well as protein levels of CTGF and TGF-βRII were measured in control (C), diabetic (D), and insulin-treated diabetic (D+I) rats. Renal B2KR and TGF-β mRNA levels expressed relative to β-actin mRNA levels and CTGF and TGF-βRII protein levels were significantly increased in D and D+I rats compared with C rats ( P < 0.03, n = 5). To assess the contribution of B2KR activation on modulating the expression of CTGF, TGF-βRII, and collagen I, mesangial cells (MC) were treated with BK (10−8 M) for 24 h and CTGF and TGF-βRII protein levels were measured by Western blots and collagen I mRNA levels were measured by RT-PCR. A two- to threefold increase in CTGF and TGF-βRII protein levels was observed in response to BK stimulation ( P < 0.001, n = 6). In addition, a marked increase in collagen I mRNA levels was observed in response to BK stimulation. Treatment of MC with BK (10−8 M) for 5 min significantly increased the tyrosine phosphorylation of p60src kinase and of p42/p44 MAPK ( P < 0.05, n = 4). Inhibition of src kinase by PP1 (10 μM) inhibited the increase in p42/p44 MAPK activation in response to BK. Finally, to determine whether BK stimulates CTGF, TGF-βRII, and collagen I expression via activation of MAPK pathways, MC were pretreated with an inhibitor of p42/p44 MAPK (PD-98059) for 45 min, followed by BK (10−8 M) stimulation for 24 h. Selective inhibition of p42/p44 MAPK significantly inhibited the BK-induced increase in CTGF, TGF-βRII, and collagen I levels. These findings are the first to demonstrate that BK regulates the expression of CTGF, TGF-βRII, and collagen I in MC and provide a mechanistic pathway through which B2KR activation may contribute to the development of diabetic nephropathy.

Group II phospholipase A2 as an autocrine growth factor mediating interleukin-1 action on mesangial cells

1997 ◽  
Vol 1345 (1) ◽  
pp. 99-108 ◽  
Author(s):  
Akira Wada ◽  
Hiromasa Tojo ◽  
Toshihiro Sugiura ◽  
Yoshihiro Fujiwara ◽  
Takenobu Kamada ◽  
...  
Keyword(s):  
Growth Factor ◽  
Phospholipase A2 ◽  
Mesangial Cells ◽  
Interleukin 1 ◽  
Autocrine Growth ◽  
Autocrine Growth Factor ◽  
Group Ii
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