Activation of extracellular signal-regulated kinases is essential for pressure-induced proliferation of vascular smooth muscle cells

Tsuda, Yuki; Okazaki, Masahiro; Uezono, Yasuhito; Osajima, Akihiko; Katô, Hiroaki; Okuda, Haruhito; Oishi, Yosuke; Yashiro, Akira; Nakashima, Yasuhide

doi:10.1016/s0014-2999(02)01811-3

Cited by 20 publications

(23 citation statements)

References 33 publications

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“…Conversely, Hsu et al (22) have reported that phagocytosis enhanced by polysaccharide from Ganoderma lucidum in neutrophils is mediated by p38 MAPK, phosphatidylinositol 3-kinase, and protein kinase C (22). Mechanical stimuli caused by stretch or pressure have been reported to activate p38 MAPK in some types of cells (2,4,44,75,76,80). Our current data suggest that increased p38 MAPK activation in response to extracellular pressure leads to pressure-induced phagocytosis by THP-1 macrophages as well as in primary isolated human peripheral monocytes.…”

Section: Discussionmentioning

confidence: 99%

“…ERK is typically activated by mechanical forces in such other types of cells as osteoblasts (27), smooth muscle cells (34,75), skeletal muscle fibers (33), intestinal epithelial cells (40,77), cardiac fibroblasts (81), and cardiac myocytes (45). However, ERK is not activated by pressure in malignant colonocytes in suspension (73) or in rat neonatal cardiac fibroblasts expressing prominent stress fibers and high basal levels of smooth muscle actin (81).…”

Section: Discussionmentioning

confidence: 99%

“…Although focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK) are activated by physical force caused by pressure in some other cell types (2,4,44,75,76,80), the effect of pressure on macrophage phagocytosis appears partially mediated by inhibition of a FAK-ERK signal pathway (67). Like ERK, the mitogen-activated protein kinase (MAPK) p38 is activated by various stress stimuli, including lipopolysaccharide (LPS) stimulation in macrophages and physical forces in various other cell types (43,44,53,55,58,72,75,76). We therefore hypothesized that changes in extracellular pressure might modulate p38 MAPK activation and that such modulation might contribute to the regulation of macrophage phagocytosis by changes in extracellular pressure during inflammation or infection.…”

mentioning

confidence: 99%

“…We therefore examined the effects of constant low pressure (20 mmHg) on macrophage phagocytosis by studying human primary isolated peripheral monocytes and monocyte-derived macrophages (MDM) as well as PMAdifferentiated (macrophage-like) human THP-1 monocytic cells in which we had previously described pressure-increased phagocytosis (67). p38 MAPK is activated by microbial phagocytosis in phagocytic cells (50,58) and in response to mechanical stimuli, such as pressure and strain in some other types of cells (2,4,44,75,76,80), and activates downstream kinases mediating inflammatory reactions (3,55,72). In this study, we examined the involvement of p38 MAPK activation by pressure in THP-1 macrophage and human monocyte phagocytosis.…”

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confidence: 99%

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Activation of p38 MAPKα by extracellular pressure mediates the stimulation of macrophage phagocytosis by pressure

Shiratsuchi¹,

Basson²

2005

American Journal of Physiology-Cell Physiology

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We have previously demonstrated that constant 20 mmHg extracellular pressure increases serumopsonized latex bead phagocytosis by phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophages in part by inhibiting focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK). Because p38 MAPK is activated by physical forces in other cells, we hypothesized that modulation of p38 MAPK might also contribute to the stimulation of macrophage phagocytosis by pressure. We studied phagocytosis in PMA-differentiated THP-1 macrophages, primary human monocytes, and human monocyte-derived macrophages (MDM). p38 MAPK activation was inhibited using SB-203580 or by p38 MAPK␣ small interfering RNA (siRNA). Pressure increased phagocytosis in primary monocytes and MDM as in THP-1 cells. Increased extracellular pressure for 30 min increased phosphorylated p38 MAPK by 46.4 Ϯ 20.5% in DMSO-treated THP-1 macrophages and by 20.9 Ϯ 9% in primary monocytes (P Ͻ 0.05 each). SB-203580 (20 M) reduced basal p38 MAPK phosphorylation by 34.7 Ϯ 2.1% in THP-1 macrophages and prevented pressure activation of p38. p38 MAPK␣ siRNA reduced total p38 MAPK protein by 50 -60%. Neither SB-203580 in THP-1 cells and peripheral monocytes nor p38 MAPK siRNA in THP-1 cells affected basal phagocytosis, but each abolished pressure-stimulated phagocytosis. SB-203580 did not affect basal or pressure-reduced FAK activation in THP-1 macrophages, but significantly attenuated the reduction in ERK phosphorylation associated with pressure. p38 MAPK␣ siRNA reduced total FAK protein by 40 -50%, and total ERK by 10 -15%, but increased phosphorylated ERK 1.4 Ϯ 0.1-fold. p38 MAPK␣ siRNA transfection did not affect the inhibition of FAK-Y397 phosphorylation by pressure but prevented inhibition of ERK phosphorylation. Changes in extracellular pressure during infection or inflammation regulate macrophage phagocytosis by a FAKdependent inverse effect on p38 MAPK␣ that might subsequently downregulate ERK.force; inflammation; infection; leukocyte; mechanotransduction; signal transduction MONOCYTES AND MACROPHAGES are recruited to sites of inflammation and play critical roles in innate host defense mechanisms. Tissue pressure is often altered in association with inflammation or infection. Mechanical stimuli such as pressure are known to modulate cellular morphology and function in other cell types (7,38,39,73,79). We have previously reported that constant low extracellular pressure increases phagocytosis by phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophages (67). Although focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK) are activated by physical force caused by pressure in some other cell types (2,4,44,75,76,80), the effect of pressure on macrophage phagocytosis appears partially mediated by inhibition of a FAK-ERK signal pathway (67). Like ERK, the mitogen-activated protein kinase (MAPK) p38 is activated by various stress stimuli, including lipopolysaccharide (LPS) stimulation in macrophages and physical force...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Activation of p38 MAPKα by extracellular pressure mediates the stimulation of macrophage phagocytosis by pressure

Shiratsuchi¹,

Basson²

2005

American Journal of Physiology-Cell Physiology

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“…18 The cells were maintained in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% FBS (GIBCO/BRL) at 37°C in a CO 2 incubator. When phosphorylation of MAPKs was examined, the concentration of FBS in DMEM was reduced to 0.5%.…”

Section: Cultured Rat Aortic Smcsmentioning

confidence: 99%

Vascular Neuronal NO Synthase Is Selectively Upregulated by Platelet-Derived Growth Factor

Nakata

Tsutsui

Shimokawa³

et al. 2005

ATVB

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Objective-We demonstrated recently that neuronal NO synthase (NOS) is expressed in arteriosclerotic lesions and exerts important vasculoprotective effects in vivo. In this study, we examined the molecular mechanism(s) for vascular neuronal NOS (nNOS) expression. Methods and Results-In cultured rat aortic smooth muscle cells, treatment with platelet-derived growth factor (PDGF) selectively upregulated nNOS expression but not inducible NOS (iNOS) or endothelial NOS (eNOS) expression. Treatment with PDGF also significantly caused activation of mitogen-activated protein kinase (MAPK) family, including extracellular signal-regulated kinase (ERK), p38MAPK, and c-Jun N-terminal kinase (JNK). ERK kinase (MAPK kinase [MEK]) inhibitors inhibited PDGF-induced nNOS expression, whereas a p38MAPK inhibitor or JNK inhibitor was without effects. Importantly, gene transfer of MEK per se elicited nNOS induction, and gene transfer of dominant-negative MEK abolished PDGF-induced nNOS expression. In isolated aortas of wild-type, eNOS Ϫ/Ϫ , and iNOS Ϫ/Ϫ mice, but not in those of nNOS Ϫ/Ϫ mice, treatment with PDGF significantly enhanced nNOS expression and nitrite plus nitrate production, both of which were again attenuated by a MEK inhibitor. Conclusions-These results provide the first evidence that vascular nNOS expression is upregulated selectively in responseto PDGF through the MEK/ERK pathway. Upregulated nNOS may play an important compensatory role under arteriosclerotic/inflammatory conditions associated with eNOS dysfunction to maintain vascular homeostasis. Key Words: ERK Ⅲ mitogen-activated protein kinase Ⅲ neuronal nitric oxide synthase Ⅲ nitric oxide Ⅲ platelet-derived growth factor N O has multiple important actions that contribute to the maintenance of vascular homeostasis. [1][2][3][4] NO is synthesized by 3 different isoforms of NO synthase (NOS): neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS). eNOS and nNOS are constitutively expressed mainly in endothelial cells and nitrergic nerves, respectively, synthesizing a small amount of NO in a calcium-dependent manner either under basal conditions or on stimulation. [1][2][3][4] In contrast, iNOS is expressed by inflammatory stimuli such as microbial endotoxins and certain proinflammatory cytokines, producing a large amount of NO in a calcium-independent manner. [1][2][3][4] Although the roles of eNOS 5-8 and iNOS 8 -11 in the development of arteriosclerosis have been investigated extensively, little is known about the role of nNOS. We demonstrated recently that nNOS also exerts important vasculoprotective effects in vivo. 12,13 In a carotid artery ligation model, nNOS Ϫ/Ϫ mice exhibited accelerated neointimal formation and constrictive vascular remodeling caused by blood flow disruption. 12,13 In a rat balloon injury model, selective inhibition of nNOS activity potently enhanced vasoconstrictor responses to calcium-mobilizing stimuli, and exacerbated neointimal formation. 12,13 In these models, nNOS was upregulated in vascular lesions and was expre...

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Inhibition of human embryonic stem cell differentiation by mechanical strain

Saha

Jiang

Pablo

et al. 2005

Journal Cellular Physiology

147

115

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Mechanical forces have been reported to induce proliferation and/or differentiation in many cell types, but the role of mechanotransduction during embryonic stem cell fate decisions is unknown. To ascertain the role of mechanical strain in human embryonic stem cell (hESC) differentiation, we measured the rate of hESC differentiation in the presence and absence of biaxial cyclic strain. Above a threshold of 10% cyclic strain, applied to a deformable elastic substratum upon which the hESC colonies were cultured, hESC differentiation was reduced and self-renewal was promoted without selecting against survival of differentiated or undifferentiated cells. Frequency of mechanical strain application had little effect on extent of differentiation. hESCs cultured under cyclic strain retained pluripotency, evidenced by their ability to differentiate to cell lineages in all three germ layers. Mechanical inhibition of hESC differentiation could not be traced to secretion of chemical factors into the media suggesting that mechanical forces may directly regulate hESC differentiation. Mechanical strain is not sufficient to inhibit differentiation, however, in unconditioned medium, hESCs grown under strain differentiated at the same rate as cells cultured in the absence of strain. Thus, while mechanical forces play a role in regulating hESC self-renewal and differentiation, they must act synergistically with chemical signals. These findings imply that application of mechanical forces may be useful, in combination with chemical and matrix-encoded signals, towards controlling differentiation of hESCs for therapeutic applications.

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Activation of extracellular signal-regulated kinases is essential for pressure-induced proliferation of vascular smooth muscle cells

Cited by 20 publications

References 33 publications

Activation of p38 MAPKα by extracellular pressure mediates the stimulation of macrophage phagocytosis by pressure

Activation of p38 MAPKα by extracellular pressure mediates the stimulation of macrophage phagocytosis by pressure

Vascular Neuronal NO Synthase Is Selectively Upregulated by Platelet-Derived Growth Factor

Inhibition of human embryonic stem cell differentiation by mechanical strain

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