scholarly journals Inhibitory effects of adiponectin on platelet-derived growth factor-induced mesangial cell migration

2009 ◽  
Vol 202 (2) ◽  
pp. 309-316 ◽  
Author(s):  
Keisuke Ishizawa ◽  
Narantungalag Dorjsuren ◽  
Yuki Izawa-Ishizawa ◽  
Rika Sugimoto ◽  
Yasumasa Ikeda ◽  
...  
Keyword(s):  
Cell Migration ◽  
Growth Factor ◽  
Map Kinase ◽  
Intracellular Signaling ◽  
Mesangial Cell ◽  
Kinase Inhibitor ◽  
P38 Map Kinase ◽  
Platelet Derived Growth Factor ◽  
Dependent Manner ◽  
Plasma Adiponectin

Adiponectin, an adipocyte-derived hormone, has been involved in metabolic syndrome, a known risk factor for the development of chronic kidney disease (CKD). Recent studies have demonstrated that plasma adiponectin levels are elevated when kidney function declines in patients with CKD. Excessive mesangial cell (MC) turnover is one of the important features of CKD. The aim of the present study is to elucidate the effects of adiponectin on platelet-derived growth factor (PDGF)-induced cell migration and intracellular signaling pathways, in cultured rat MCs (RMCs). PDGF-induced RMC migration was significantly inhibited by the pretreatment of adiponectin. Adiponectin alone had no effect on RMC migration. Big mitogen-activated protein (MAP) kinase 1 (BMK1), p38 MAP kinase, and Akt were activated by PDGF stimulation in a time- and concentration-dependent manner in RMC. Adiponectin alone did not affect BMK1, p38 MAP kinase, and Akt phosphorylations in RMC. PDGF-induced BMK1 and p38 MAP kinase phosphorylations were significantly attenuated by the pretreatment of adiponectin in RMCs. On the other hand, the phosphorylation of Akt by PDGF was not diminished by the pretreatment of adiponectin. Adiponectin had no effects on PDGF-receptor autophosphorylation by PDGF. We also confirmed that PDGF-induced RMC migration was significantly suppressed by siBMK1 transfection or SB203580, a p38 MAP kinase inhibitor. From these findings, it is implied that the elevated plasma adiponectin levels in patients with CKD might play a compensatory role aimed at counteracting renal dysfunction related to MC disorders.

scholarly journals Regulation of Rat Mesangial Cell Migration by Platelet-Derived Growth Factor, Angiotensin II, and Adrenomedullin

1999 ◽  
Vol 10 (12) ◽  
pp. 2495-2502 ◽  
Author(s):  
MASAKAZU KOHNO ◽  
KENICHI YASUNARI ◽  
MIEKO MINAMI ◽  
HIROAKI KANO ◽  
KENSAKU MAEDA ◽  
...  
Keyword(s):  
Cell Migration ◽  
Angiotensin Ii ◽  
Growth Factor ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Inhibitory Effect ◽  
Platelet Derived Growth Factor ◽  
Dependent Manner ◽  
Glomerular Mesangial Cells ◽  
Concentration Dependent Manner

Abstract. This study sought to determine whether platelet-derived growth factor (PDGF) and angiotensin II (AngII) stimulate migration of cultured rat glomerular mesangial cells. After finding that this was so, the effects of adrenomedullin (ADM) and cAMP-elevating agents on basal and stimulated mesangial cell migration were examined. Two isoforms of PDGF, AB and BB, stimulated migration in a concentration-dependent manner between 1 and 50 ng/ml, while the AA isoform lacked significant effect. AngII modestly but significantly stimulated migration in a concentration-dependent manner between 10-7 and 10-6 mol/L. Rat ADM significantly inhibited the PDGF BB- and AngII-stimulated migration in a concentration-dependent manner between 10-8 and 10-7 mol/L. Inhibition by rat ADM was accompanied by an increase in cellular cAMP. cAMP agonists or inducers such as 8-bromo cAMP, forskolin, and prostaglandin I2 also significantly reduced the stimulated migration. H 89, a protein kinase A (PKA) inhibitor, attenuated the inhibitory effect of ADM, and a calcitonin gene-related peptide (CGRP) receptor antagonist, human CGRP (8-37), abolished the inhibitory effects of rat ADM. These results suggest that PDGF AB and BB as well as AngII stimulate rat mesangial cell migration and that ADM can inhibit PDGF BB- and AngII-stimulated migration, at least in part through cAMP-dependent mechanisms likely to involve specific ADM receptors with which CGRP interacts. The adenylate cyclase/cAMP/PKA system may be involved in the migration-inhibitory effect of ADM in these cells.

scholarly journals Resveratrol Inhibits the Epidermal Growth Factor-Induced Migration of Osteoblasts: the Suppression of SAPK/JNK and Akt

2017 ◽  
Vol 43 (3) ◽  
pp. 1025-1036 ◽  
Author(s):  
Tetsu Kawabata ◽  
Haruhiko Tokuda ◽  
Kazuhiko Fujita ◽  
Shingo Kainuma ◽  
Go Sakai ◽  
...  
Keyword(s):  
Cell Migration ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Map Kinase ◽  
Rho Kinase ◽  
Inhibitory Effect ◽  
P38 Map Kinase ◽  
Boyden Chamber ◽  
Dependent Manner ◽  
Epidermal Growth

Background/Aims: Resveratrol is a polyphenol enriched in the skins of grapes and berries, that shows various beneficial effects for human health. In the present study, we investigated the mechanism behind the epidermal growth factor (EGF)-induced migration of osteoblast-like MC3T3-E1 cells, and the effect of resveratrol on this cell migration. Methods: The cell migration was examined using Boyden chamber, and phosphorylation of each kinase was analyzed by Western blotting. Results: The EGF-induced migration was suppressed by PD98059, an inhibitor of MEK1/2, as well as SB203580, an inhibitor of p38 MAP kinase, SP600125, an inhibitor of SAPK/JNK, and deguelin, an inhibitor of Akt. In contrast, rapamycin, an inhibitor of upstream kinase of p70 S6 kinase, and fasudil, an inhibitor of Rho-kinase, hardly affected the migration. Resveratrol significantly reduced the EGF-induced migration in a dose-dependent manner. SRT1720, an SIRT1 activator, suppressed the migration by EGF. In addition, resveratrol markedly attenuated the EGF-induced phosphorylation of SAPK/JNK and Akt without affecting the phosphorylation of p44/p42 MAP kinase or p38 MAP kinase. The phosphorylation of SAPK/JNK and Akt induced by EGF was down-regulated by SRT1720. Conclusion: Our results strongly suggest that resveratrol reduces the EGF-stimulated migration of osteoblasts via suppression of SAPK and Akt, and that the inhibitory effect of resveratrol is mediated in part via SIRT1.

scholarly journals Stimulation of cardiac fibroblast Piezo1 channels opposes myofibroblast differentiation and induces IL-6 secretion via Ca2+-mediated p38 MAP kinase activation

2019 ◽  
Author(s):  
Nicola M. Blythe ◽  
Vasili Stylianidis ◽  
Melanie J. Ludlow ◽  
Hamish T. J. Gilbert ◽  
Elizabeth L. Evans ◽  
...  
Keyword(s):  
Map Kinase ◽  
Structural Integrity ◽  
Kinase Inhibitor ◽  
Cardiac Fibroblasts ◽  
Collagen Gel ◽  
Mechanical Stretch ◽  
Cardiac Fibroblast ◽  
Ruthenium Red ◽  
P38 Map Kinase ◽  
Dependent Manner

AbstractPiezo1 is a mechanosensitive cation channel with widespread physiological importance; however its role in the heart is poorly understood. Cardiac fibroblasts are responsible for preserving the structural integrity of the myocardium and play a key role in regulating its repair and remodeling following stress or injury. We investigated expression and function of Piezo1 in cultured human and mouse cardiac fibroblasts. RT-PCR studies confirmed expression ofPiezo1mRNA in cardiac fibroblasts at similar levels to endothelial cells. Fura-2 intracellular Ca2+measurements validated Piezo1 as a functional ion channel that was activated by the Piezo1 agonist, Yoda1. Yoda1-induced Ca2+entry was inhibited by Piezo1 blockers (gadolinium, ruthenium red) and the Ca2+response was reduced proportionally by Piezo1 siRNA knockdown or in cells fromPiezo1+/−mice. Investigation of Yoda1 effects on selected remodeling genes indicated that Piezo1 activation opposed cardiac fibroblast differentiation; data confirmed by functional collagen gel contraction assays. Piezo1 activation using Yoda1 or mechanical stretch also increased the expression of interleukin-6 (IL-6), a mechanosensitive pro-hypertrophic and pro-fibrotic cytokine, in a Piezo1-dependent manner. Multiplex kinase activity profiling combined with kinase inhibitor studies and phospho-specific western blotting, established that Piezo1 activation stimulated IL-6 secretion via a pathway involving p38 MAP kinase, downstream of Ca2+entry. In summary, this study reveals that cardiac fibroblasts express functional Piezo1 channels coupled to reduced myofibroblast activation and increased secretion of paracrine signaling molecules that can modulate cardiac remodeling.

p38 MAP kinase negatively regulates cyclin D1 expression in airway smooth muscle cells

2001 ◽  
Vol 280 (5) ◽  
pp. L955-L964 ◽  
Author(s):  
Kristen Page ◽  
Jing Li ◽  
Marc B. Hershenson
Keyword(s):  
Growth Factor ◽  
Map Kinase ◽  
Cyclin D1 ◽  
Growth Regulation ◽  
P38 Map Kinase ◽  
Dominant Negative ◽  
Platelet Derived Growth Factor ◽  
Airway Smooth Muscle Cells ◽  
Erk Activation ◽  
Erk Phosphorylation

We have demonstrated that platelet-derived growth factor (PDGF) stimulates p38 mitogen-activated protein (MAP) kinase activation in bovine tracheal myocytes, suggesting that p38 is involved in growth regulation. We therefore examined whether p38 regulates expression of cyclin D1, a G1 cyclin required for cell cycle traversal. The chemical p38 inhibitors SB-202190 and SB-203580 each increased basal and PDGF-induced cyclin D1 promoter activity and protein abundance. Overexpression of a dominant negative allele of MAP kinase kinase-3 (MKK3), an upstream activator of p38α, had similar effects. Conversely, active MKK3 and MKK6, both of which increase p38α activity, each decreased transcription from the cyclin D1 promoter. Together, these data demonstrate that p38 negatively regulates cyclin D1 expression. We tested whether p38 regulates cyclin D1 expression via inhibition of extracellular signal-regulated kinase (ERK) activation. Chemical inhibitors of p38 induced modest ERK phosphorylation and activation. However, dominant negative MKK3 was insufficient to activate ERK, and active MKK3 and MKK6 did not attenuate platelet-derived growth factor-mediated ERK activation. These data are consistent with the notion that p38α negatively regulates cyclin D1 expression via an ERK-independent pathway.

scholarly journals Mechanisms underlying modulation of monocarboxylate transporter 1 (MCT1) by somatostatin in human intestinal epithelial cells

2009 ◽  
Vol 297 (5) ◽  
pp. G878-G885 ◽  
Author(s):  
Seema Saksena ◽  
Saritha Theegala ◽  
Nikhil Bansal ◽  
Ravinder K. Gill ◽  
Sangeeta Tyagi ◽  
...  
Keyword(s):  
Map Kinase ◽  
Kinase Inhibitor ◽  
Apical Membrane ◽  
P38 Map Kinase ◽  
Monocarboxylate Transporter ◽  
Maximal Velocity ◽  
Dependent Manner ◽  
Intestinal Epithelial ◽  
Human Intestine ◽  
Monocarboxylate Transporter 1

Somatostatin (SST), an important neuropeptide of the gastrointestinal tract has been shown to stimulate sodium chloride absorption and inhibit chloride secretion in the intestine. However, the effects of SST on luminal butyrate absorption in the human intestine have not been investigated. Earlier studies from our group and others have shown that monocarboxylate transporter (MCT1) plays an important role in the transport of butyrate in the human intestine. The present studies were undertaken to examine the effects of SST on butyrate uptake utilizing postconfluent human intestinal epithelial Caco2 cells. Apical SST treatment of Caco-2 cells for 30–60 min significantly increased butyrate uptake in a dose-dependent manner with maximal increase at 50 nM (∼60%, P < 0.05). SST receptor 2 agonist, seglitide, mimicked the effects of SST on butyrate uptake. SST-mediated stimulation of butyrate uptake involved the p38 MAP kinase-dependent pathway. Kinetic studies demonstrated that SST increased the maximal velocity ( Vmax) of the transporter by approximately twofold without any change in apparent Michaelis-Menten constant ( Km). The higher butyrate uptake in response to SST was associated with an increase in the apical membrane levels of MCT1 protein parallel to a decrease in the intracellular MCT1 pool. MCT1 has been shown to interact specifically with CD147 glycoprotein/chaperone to facilitate proper expression and function of MCT1 at the cell surface. SST significantly enhanced the membrane levels of CD147 as well as its association with MCT1. This association was completely abolished by the specific p38 MAP kinase inhibitor, SB203580. Our findings demonstrate that increased MCT1 association with CD147 at the apical membrane in response to SST is p38 MAP kinase dependent and underlies the stimulatory effects of SST on butyrate uptake.

scholarly journals p38 MAP Kinase Inhibitor Suppresses Transforming Growth Factor-β2–Induced Type 1 Collagen Production in Trabecular Meshwork Cells

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0120774 ◽  
Author(s):  
Miyuki Inoue-Mochita ◽  
Toshihiro Inoue ◽  
Tomokazu Fujimoto ◽  
Takanori Kameda ◽  
Nanako Awai-Kasaoka ◽  
...  
Keyword(s):  
Growth Factor ◽  
Map Kinase ◽  
Trabecular Meshwork ◽  
Transforming Growth Factor ◽  
Kinase Inhibitor ◽  
P38 Map Kinase ◽  
Collagen Production ◽  
Trabecular Meshwork Cells ◽  
Transforming Growth Factor Β2

scholarly journals Separating myoblast differentiation from muscle cell fusion using IGF-I and the p38 MAP kinase inhibitor SB202190

2015 ◽  
Vol 309 (7) ◽  
pp. C491-C500 ◽  
Author(s):  
Samantha Gardner ◽  
Sean M. Gross ◽  
Larry L. David ◽  
John E. Klimek ◽  
Peter Rotwein
Keyword(s):  
Growth Factor ◽  
Map Kinase ◽  
Cell Fusion ◽  
Muscle Cell ◽  
Map Kinases ◽  
Kinase Inhibitor ◽  
P38 Map Kinase ◽  
Myoblast Differentiation ◽  
Igf I ◽  
Muscle Biology

The p38 MAP kinases play critical roles in skeletal muscle biology, but the specific processes regulated by these kinases remain poorly defined. Here we find that activity of p38α/β is important not only in early phases of myoblast differentiation, but also in later stages of myocyte fusion and myofibrillogenesis. By treatment of C2 myoblasts with the promyogenic growth factor insulin-like growth factor (IGF)-I, the early block in differentiation imposed by the p38 chemical inhibitor SB202190 could be overcome. Yet, under these conditions, IGF-I could not prevent the later impairment of muscle cell fusion, as marked by the nearly complete absence of multinucleated myofibers. Removal of SB202190 from the medium of differentiating myoblasts reversed the fusion block, as multinucleated myofibers were detected several hours later and reached ∼90% of the culture within 30 h. Analysis by quantitative mass spectroscopy of proteins that changed in abundance following removal of the inhibitor revealed a cohort of upregulated muscle-enriched molecules that may be important for both myofibrillogenesis and fusion. We have thus developed a model system that allows separation of myoblast differentiation from muscle cell fusion and should be useful in identifying specific steps regulated by p38 MAP kinase-mediated signaling in myogenesis.

Expression of CCN1 (CYR61) in developing, normal, and diseased human kidney

2007 ◽  
Vol 293 (4) ◽  
pp. F1363-F1372 ◽  
Author(s):  
Kazutomo Sawai ◽  
Masashi Mukoyama ◽  
Kiyoshi Mori ◽  
Masato Kasahara ◽  
Masao Koshikawa ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Mesangial Cell ◽  
Kinase Inhibitor ◽  
Human Kidney ◽  
Thick Ascending Limb ◽  
Dependent Manner ◽  
Glomerular Injury ◽  
Mesangial Expansion

CCN1 (cysteine-rich protein 61; Cyr61) is an extracellular matrix-associated signaling molecule that functions in cell migration, adhesion, and differentiation. We previously reported that CCN1 is induced at podocytes in rat anti-Thy-1 glomerulonephritis, a well-known model of reversible glomerular injury, but its expression and significance in the human kidney remain totally unknown (Sawai K, Mori K, Mukoyama M, Sugawara A, Suganami T, Koshikawa M, Yahata K, Makino H, Nagae T, Fujinaga Y, Yokoi H, Yoshioka T, Yoshimoto A, Tanaka I, Nakao K. J Am Soc Nephrol 14: 1154–1163, 2003). Here we report that, in the human kidney, CCN1 expression was confined to podocytes in normal adult and embryonic glomeruli from the capillary loop stage. Podocyte CCN1 expression was decreased in IgA nephropathy, diabetic nephropathy, and membranous nephropathy, whereas it remained unchanged in minimal change disease and focal segmental glomerulosclerosis. Downregulation of CCN1 was significantly greater in diseased kidneys with severe mesangial expansion. CCN1 protein was also localized in the thick ascending limb of Henle's loop, distal and proximal tubules, and collecting ducts, which was not altered in diseased kidneys. In vitro, recombinant CCN1 protein enhanced endothelial cell adhesion, whereas it prominently inhibited mesangial cell adhesion. CCN1 also completely suppressed mesangial cell migration, suggesting its role as a mesangial-repellent factor. In cultured podocytes, CCN1 markedly induced the expression of cyclin-dependent kinase inhibitor p27Kip1 as well as synaptopodin in a dose-dependent manner and suppressed podocyte migration. These data indicate that CCN1 is expressed in podocytes, can act on glomerular cells to modulate glomerular remodeling, and is downregulated in diseased kidneys, suggesting that impairment of CCN1 expression in podocytes may contribute to the progression of glomerular disease with mesangial expansion.

scholarly journals (-)-Epigallocatechin Gallate Reduces Platelet-Derived Growth Factor-BB-Stimulated Interleukin-6 Synthesis in Osteoblasts: Suppression of SAPK/JNK

2008 ◽  
Vol 2008 ◽  
pp. 1-8 ◽  
Author(s):  
Shinji Takai ◽  
Rie Matsushima-Nishiwaki ◽  
Seiji Adachi ◽  
Hideo Natsume ◽  
Chiho Minamitani ◽  
...  
Keyword(s):  
Growth Factor ◽  
Map Kinase ◽  
Interleukin 6 ◽  
Epigallocatechin Gallate ◽  
P38 Map Kinase ◽  
Platelet Derived Growth Factor ◽  
S6 Kinase ◽  
Jnk Pathway ◽  
P70 S6 Kinase ◽  
Mitogen Activated Protein

We previously showed that the mitogen-activated protein (MAP) kinase superfamily, p44/p42 MAP kinase, p38 MAP kinase, and stress-activated protein kinase (SAPK)/c-JunN-terminal (JNK), positively plays a part in the platelet-derived growth factor-BB- (PDGF-BB-) stimulated synthesis of interleukin-6 (IL-6), a potent bone resorptive agent, in osteoblast-like MC3T3-E1 cells while Akt and p70 S6 kinase negatively regulates the synthesis. In the present study, we investigated whether (-)-epigallocatechin gallate (EGCG), one of the major green tea flavonoids, affects the synthesis of IL-6 in these cells and the mechanism. EGCG significantly reduced the IL-6 synthesis and IL-6 mRNA expression stimulated by PDGF-BB, EGCG reduced the PDGF-BB-stimulated IL-6 synthesis also in primary-cultured osteoblasts. EGCG had no effect on the levels of osteocalcin and osteoprotegerin in MC3T3-E1 cells. The PDGF-BB-induced autophosphorylation of PDGF receptorβwas not suppressed by EGCG. The PDGF-BB-induced phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was not affected by EGCG. On the other hand, EGCG markedly suppressed the PDGF-BB-induced phosphorylation of SAPK/JNK. Finally, the PDGF-BB-induced phosphorylation of Akt and p70 S6 kinase was not affected by EGCG. These results strongly suggest that EGCG inhibits the PDGF-BB-stimulated synthesis of IL-6 via suppression of SAPK/JNK pathway in osteoblasts.

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