scholarly journals PSII-6 Lysine-induced stimulation of proliferation, differentiation and migration in swine satellite cells is mediated by the mTORC1 and FAK pathways.

2018 ◽  
Vol 96 (suppl_3) ◽  
pp. 77-77
Author(s):  
C Jin ◽  
C Gao ◽  
Z Zhang ◽  
H Yan ◽  
X Wang
Keyword(s):  
Satellite Cells ◽  
And Migration ◽  
Stimulation Of

Abstract 1359: Only the Catalytic p110alpha Isoform Mediates Class IA PI 3-Kinase-Induced Atherogenic Signals in Vascular Smooth Muscle Cells

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Marius Vantler ◽  
Lenard Mustafov ◽  
Evren Caglayan ◽  
Stephan Rosenkranz
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Dna Synthesis ◽  
Vascular Smooth Muscle Cells ◽  
Fold Increase ◽  
And Migration ◽  
Induced Apoptosis ◽  
Stimulation Of

Proliferation, migration, and apoptosis of vascular smooth muscle cells (VSMC) are pivotal determinants of the pathogenesis of vascular diseases, which are mainly controlled by growth factor dependent activation of PI 3-Kinase (PI3K). Growth factors like platelet-derived growth factor (PDGF) activate class IA PI3Ks containing one of three p110 catalytic subunits (p110alpha, p110beta, and p110delta). We investigated the specific function of these isoforms for PDGF-controlled proliferation, migration, and apoptosis of VSMC using novel isoform-specific inhibitors. PDGF-dependent proliferation and migration solely depended on p110alpha. Stimulation of VSMC with PDGF-BB (50 ng/ml) mediated a 2.5±0.4 increase ( p <0.05) of DNA-synthesis (BrdU incorporation assay) and induced a 3.4+/−0.7 fold increase ( p <0.05) of VSMC migration (modified Boyden-chamber). Inhibition of p110alpha with PIK075 (1 μ M, Ki=100 nM) completely abrogated PDGF-dependent DNA-synthesis and migration ( p <0,05), whereas inhibitors against p110beta (TGX 221, 1 μ M) or p110delta (IC87114 1 μ M) had no influence. Consistently, PDGF-induced DNA-synthesis and migration were suppressed by siRNA-dependent downregulation of p110alpha ( p <0,05) whereas p110beta or p110delta knockdown had no effect. Interestingly, stimulation of VSMC with PDGF-BB (50 ng/ml) induced anti- or proapoptotic effects depending on the duration of PDGFR activation. Incubation of VSMC with H 2 O 2 (50 μ M, 16h) led to a 2.8±0.7 fold increase ( p >0.05) of apoptosis (Cell Death Detection ELISA). Simultanous addition of PDGF-BB (50 ng/ml) significantly diminished the H 2 O 2 -induced apoptosis (52±7%, p >0.05). In contrast, prestimulation with PDGF-BB 24h prior to the addition of H 2 O 2 led to an increase of H 2 O 2 -induced apoptosis (7.8±1.3, p >0.05). The anti- as well as the proapoptotic effect depended strictly on p110alpha as PIK075 (1 μ M, p <0,05) or p110alpha specific siRNA completely abrogated PDGF-BB-mediated pro- as well as antiapoptotic effects. Our results demonstrate that only the catalytical PI3K subunit p110alpha mediates the growth factor-induced atherogenic responses. Therefore, p110alpha represents an interesting therapeutic target for prevention of atherosclerosis and restenosis formation.

Importance of melastatin-like transient receptor potential 7 and magnesium in the stimulation of osteoblast proliferation and migration by platelet-derived growth factor

2009 ◽  
Vol 297 (2) ◽  
pp. C360-C368 ◽  
Author(s):  
Elie Abed ◽  
Robert Moreau
Keyword(s):  
Growth Factor ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Platelet Derived Growth Factor ◽  
Human Osteoblast ◽  
Osteoblast Proliferation ◽  
Transient Receptor ◽  
And Migration ◽  
Stimulation Of ◽  
Proliferation And Migration

Bone is a dynamic tissue that is continuously being remodeled throughout life. Specialized cells called osteoclasts transiently break down old bone (resorption process) at multiple sites as other cells known as osteoblasts are replacing it with new tissue (bone formation). Usually, both resorption and formation processes are in balance and thereby maintain skeletal strength and integrity. This equilibrium is assured by the coordination of proliferation, migration, differentiation, and secretory functions of the osteoblasts, which are essential for adequate formation and resorption processes. Disturbances of this equilibrium may lead to decreased bone mass (osteoporosis), increased bone fragility, and susceptibility to fractures. Epidemiological studies have linked insufficient dietary magnesium (Mg2+) intake in humans with low bone mass and osteoporosis. Here, we investigated the roles of Mg2+ and melastatin-like transient receptor potential 7 (TRPM7), known as Mg2+ channels, in human osteoblast cell proliferation and migration induced by platelet-derived growth factor (PDGF), which has been involved in the bone remodeling process. PDGF promoted an influx of Mg2+, enhanced cell migration, and stimulated the gene expression of TRPM7 channels in human osteoblast MG-63 cells. The stimulation of osteoblast proliferation and migration by PDGF was significantly reduced under culture conditions of low extracellular Mg2+ concentrations. Silencing TRPM7 expression in osteoblasts by specific small interfering RNA prevented the induction by PDGF of Mg2+ influx, proliferation, and migration. Our results indicate that extracellular Mg2+ and TRPM7 are important for PDGF-induced proliferation and migration of human osteoblasts. Thus Mg2+ deficiency, a common condition among the general population, may be associated with altered osteoblast functions leading to inadequate bone formation and the development of osteoporosis.

scholarly journals Regulation of Na+/H+ Exchanger in Dendritic Cells by Akt1

2015 ◽  
Vol 36 (3) ◽  
pp. 1237-1249 ◽  
Author(s):  
Yuetao Zhou ◽  
Venkanna Pasham ◽  
Soumya Chatterjee ◽  
Anand Rotte ◽  
Wenting Yang ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Primary Immune Response ◽  
Cytosolic Ph ◽  
Forward Scatter ◽  
Akt Phosphorylation ◽  
Tert Butylhydroperoxide ◽  
Ros Formation ◽  
Bacterial Lipopolysaccharides ◽  
And Migration ◽  
Stimulation Of

Background/Aims: Dendritic cells (DCs), antigen-presenting cells critically important for primary immune response and establishment of immunological memory, are activated by bacterial lipopolysaccharides (LPS) resulting in stimulation of Na+/H+ exchanger, ROS formation and migration. The effects are dependent on phosphoinositide 3 (PI3) kinase and paralleled by Akt phosphorylation. The present study explored the contribution of the Akt isoform Akt1. Methods: Cytosolic pH (pHi) (2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein [BCECF] fluorescence), Na+/H+ exchanger activity (Na+ dependent realkalinization after an ammonium pulse), cell volume (forward scatter in FACS analysis), and ROS production (2′,7′-dichlorodihydrofluorescein diacetate [DCFDA] fluorescence) were determined in DCs isolated from bone marrow of mice lacking functional Akt1/PKBα (akt1-/-) and their wild type littermates (akt1+/+). Results: Forward scatter was lower in akt1-/- than in akt1+/+ DCs, whereas pHi, Na+/H+ exchanger activity and ROS formation were less in untreated akt1-/- and akt1+/+ DCs. Exposure of DCs to LPS was followed by increase of forward scatter and ROS formation to a similar extent in akt1-/- and in akt1+/+ DCs. A 4 hours treatment with either LPS (1µg/ml) or tert-butylhydroperoxide (tBOOH, 5 µM) significantly stimulated Na+/H+ exchanger activity in both genotypes, effects, however, significantly blunted in akt1-/- DCs. Conclusion: The present observations demonstrate that Akt1 is required for the full stimulation of Na+/H+ exchanger activity by LPS or oxidative stress in dendritic cells.

scholarly journals Stimulation of TLR4 by LMW-HA Induces Metastasis in Human Papillary Thyroid Carcinoma through CXCR7

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Shipeng Dang ◽  
Yongde Peng ◽  
Lei Ye ◽  
Yanan Wang ◽  
Zhongqing Qian ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Thyroid Tissue ◽  
Tissue Samples ◽  
Normal Tissues ◽  
Cell Proliferation And Migration ◽  
Novel Target ◽  
And Migration ◽  
Tissues Expression ◽  
Stimulation Of ◽  
Proliferation And Migration

In inflammatory sites, high molecular weight hyaluronan fragments are degraded into lower molecular weight hyaluronan fragments (LMW-HA) to regulate immune responses. However, the function of LMW-HA in PTC progression remains to be elucidated. In this study, we found that receptor of LMW-HA, TLR4, was aberrantly overexpressed in PTC tissues and cell line W3. Exposure of W3 cells to LMW-HA promoted cell proliferation and migration via TLR4. Knockdown of TLR4 has provided evidence that TLR4 is essential for LMW-HA-induced CXCR7 expression, which is responsible for LMW-HA-induced proliferation and migration of W3 cells. In tumor-bearing adult nude mice, stimulation of LMW-HA on W3 cells promotes CXCR7 expression in tumor masses (P=0.002) and tumor growth (P<0.001). To further confirm our findings, we investigated the clinicopathologic significance of TLR4 and CXCR7 expression using immumohistochemistry in 135 human PTC tissues and 56 normal thyroid tissue samples. Higher rates of TLR4 (53%) and CXCR7 (24%) expression were found in PTC tissues than in normal tissues. Expression of TLR4 or CXCR7 is associated with tumor size and lymph node metastasis. Therefore, LMW-HA may contribute to the development of PTC via TLR4/CXCR7 pathway, which may be a novel target for PTC immunomodulatory therapy.

SYK Is Involved in the CD38 Signal Transduction Pathway in Chronic Lymphocytic Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2910-2910
Author(s):  
Marco Benkisser-Petersen ◽  
Maike Buchner ◽  
Arlette Dörffel ◽  
Marcus Dühren von Minden ◽  
Kerstin Leberecht ◽  
...  
Keyword(s):  
B Cell ◽  
Signal Transduction Pathway ◽  
Lymphocytic Leukemia ◽  
Transduction Pathway ◽  
Cd38 Expression ◽  
Bcr Signaling ◽  
Syk Inhibitor ◽  
And Migration ◽  
Stimulation Of ◽  
Proliferation And Migration

Abstract B-cell chronic lymphocytic leukemia (CLL) is one of the most prevalent B cell malignancies in adults and characterized by expansion of monoclonal mature B cells. Survival and proliferation of CLL cells depends on microenvironmental contact in lymphoid organs. The transmembrane glycoprotein CD38 acts as an important mediator of survival, proliferation and migration signals for CLL cells, and its expression is associated with poor prognosis. Spleen tyrosine kinase (SYK) is a central element of the B-cell receptor signal transduction pathway and has additionally been shown to be involved in cytokine and integrine signaling. In this study we demonstrate direct involvement of SYK in the CD38 signaling pathway in primary CLL samples. CD38-stimulation of primary CLL cells by its ligand CD31 induced a consistent phosphorylation of the tyrosine residue Y352, the first activation site that releases SYK from its autoinhibitory conformation (p<0.001). SYK downstream targets AKT (p<0.05) and ERK (p<0.05) were subsequently induced and prolonged CD38-stimulation increased MCL-1-expression (p<0.05). Concomitant inhibition of SYK with the SYK inhibitor R406 resulted in inhibition of AKT- and ERK-activation (p<0.05 and p<0.01) and prevented upregulation of MCL-1 (p<0.01). Moreover, we observed SYK-dependent enhancement of BCR-signaling after CD38 ligation. Short-term exposure of CLL cells to CD31 led to an increase of ERK-phosphorylation after BCR-engagement by 41.9% (p<0.05). This effect was completely abolished by concomitant R406-treatment (p<0.05). Additionally, we observed a SYK-dependent increase of Ca2+-flux in response to BCR-stimulation after previous CD38 activation. Moreover, preliminary experiments show that prolonged CD38-stimulation led to a SYK-dependent increase of baseline Ca2+-flux in CLL cells, indicating a potential involvement of CD38 in autonomous BCR-signaling. CD38 acts as an enhancer of migratory stimuli in CLL cells. We therefore analysed, whether SYK is also involved in this interaction process. CXCL12-dependent migration was increased by CD38 stimulation with the agonistic CD38 antibody IB4 by 28.3% (p=0.12). Treatment of CLL cells with R406 completely inhibited IB4-mediated migration (p<0.01). The expression of CD38 is regulated by a variety of mechanisms, including CD40 ligation. SYK is involved in CD40 signaling. We therefore tested, whether SYK-inhibition affects CD38-expression. Stimulation of CLL cells with recombinant CD40L resulted in a significant increase of CD38-expression (p<0.05). This effect was reversed by concomitant SYK-inhibition (p<0.01). In addition, we observed marked down-regulation of CD38 surface-expression (p<0.05) and mRNA-expression (p<0.05) for CLL cells treated with SYK-inhibitors R406 or P505-15 compared to vehicle control. This effect is at least partly based on transcriptional inhibition of CD38-regulators NF-kB (p<0.05) and E2A (p<0.05). Finally, we observed a clear correlation between CD38 expression on CLL cells and SYK-inhibitor efficacy (p<0.01). In conclusion, our data show that SYK acts as a central downstream effector of CD38 signaling regulating survival-, proliferation-, and migration pathways in CLL and also functions as a strong regulator of CD38 expression. The interaction of CD38 and SYK involves the BCR pathways, where CD38 enhances the response to BCR-stimulation and, moreover, may act as an enhancer of autonomous BCR-signaling in CLL. Additionally, the CD38-SYK interaction involves BCR-independent microenvironmental pathways as shown for CD40 and CXCL12. CD38 expression not only serves as a negative prognostic marker but has also been shown to possess biological significance in CLL. We therefore propose that disruption of the CD38-SYK axis may represent a promising therapeutic option in CLL. Disclosures No relevant conflicts of interest to declare.

IL-1β stimulation of CCD-18co myofibroblasts enhances repair of epithelial monolayers through Wnt-5a

2012 ◽  
Vol 303 (11) ◽  
pp. G1270-G1278 ◽  
Author(s):  
Meera Raymond ◽  
Tania Marchbank ◽  
Mary P. Moyer ◽  
Raymond J. Playford ◽  
Ian R. Sanderson ◽  
...  
Keyword(s):  
Wound Repair ◽  
Signal Transduction Pathway ◽  
Leading Edge ◽  
Conditioned Media ◽  
Intestinal Epithelial ◽  
Molecular Signaling ◽  
Epithelial Repair ◽  
Nuclear Extracts ◽  
And Migration ◽  
Stimulation Of

Subepithelial myofibroblasts are involved in the initiation and coordination of intestinal epithelial repair, but the molecular signaling pathways are largely unknown. The cellular adaptations that occur during repair range from dedifferentiation and migration to proliferation and redifferentiation, in a way that is strongly reminiscent of normal crypt-to-villus epithelial maturation. We therefore hypothesized that Wnt/β-catenin signaling may have a pivotal role in intestinal epithelial wound repair. We used the established scratch wound method in Caco-2 cells and in nontransformed NCM460 cells to monitor the effects of IL-1β-stimulated colonic myofibroblasts (CCD-18co) on intestinal epithelial repair, with immunoblotting and immunodepletion to examine the conditioned media. Conditioned media from IL-1β-stimulated, but not -untreated, myofibroblasts increased Caco-2 wound closure twofold over 24 h. IL-1β-stimulated myofibroblasts downregulated the differentiation marker sucrase-isomaltase in the Caco-2 cells, whereas the proliferation marker c-myc was upregulated. Array expression profiling identified Wnt-5a as the Wnt-related gene that was most upregulated (28-fold) by IL-1β stimulation of CCDs. Recombinant Wnt-5a enhanced proliferation of Caco-2 and NCM460 cells. In scratch assays, it increased migration of the leading edge in both cell lines. Wnt-5a immunodepletion of the IL-1β-CCD conditioned media abrogated the ability to enhance the repair. Wnt-5a often acts through a noncanonical signal transduction pathway. Further experiments supported this pathway in epithelial wound healing: IL-1β-CCD-mediated repair was not affected by the addition of the canonical Wnt antagonist Dickkopf-1. Furthermore, media from stimulated myofibroblasts (but not Wnt-5a-depleted media) increased c-jun in Caco-2 cell nuclear extracts. Myofibroblast-mediated noncanonical Wnt-5a signaling is therefore important in the dedifferentiation and migration stages of epithelial wound repair.

scholarly journals Stimulation of Proliferation and Migration of Mouse Macrophages by Type B CpG-ODNs Is F-Spondin and IL-1Ra Dependent

PLoS ONE ◽  
2015 ◽  
Vol 10 (6) ◽  
pp. e0128926 ◽  
Author(s):  
Tai-An Chen ◽  
Chiao-Chun Liao ◽  
Yung-Chih Cheng ◽  
Yen-Po Chen ◽  
Yi-Fan Hsu ◽  
...  
Keyword(s):  
Type B ◽  
Mouse Macrophages ◽  
Cpg Odns ◽  
And Migration ◽  
Stimulation Of ◽  
Proliferation And Migration

scholarly journals Autocrine stimulation of VEGFR-2 activates human leukemic cell growth and migration

2000 ◽  
Vol 106 (4) ◽  
pp. 511-521 ◽  
Author(s):  
Sergio Dias ◽  
Koichi Hattori ◽  
Zhenping Zhu ◽  
Beate Heissig ◽  
Margaret Choy ◽  
...  
Keyword(s):  
Cell Growth ◽  
Leukemic Cell ◽  
Cell Growth And Migration ◽  
Human Leukemic Cell ◽  
Autocrine Stimulation ◽  
And Migration ◽  
Stimulation Of
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