Integrins induce expression of monocyte chemoattractant protein-1 via focal adhesion kinase in mesangial cells

Watanabe, Yujiro; Tamura, Masahito; Osajima, Akihiko; Anai, Hirofumi; Kabashima, Narutoshi; Serino, Ryota; Nakashima, Yasuhide

doi:10.1046/j.1523-1755.2003.00122.x

Cited by 22 publications

(37 citation statements)

References 40 publications

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“…38 Contactdependent MCP-1 upregulation in HVSMCs may also be possible, because MCP-1 induction was observed in mesangial cells during interaction with extracellular matrix in ␤ 1 integrin-dependent manner. 39 Because MCP-1 is a potent monocyte chemoattractant, our results suggest that MCP-1 generated in the subendothelial space during monocyte/ VSMC interactions may be a key factor mediating sustained monocyte infiltration in a vicious loop. However, MCP-1 may not be the only soluble factor involved, and additional studies are needed to identify the nature of other potential mediators.…”

Section: Discussionmentioning

confidence: 93%

Interaction of Monocytes With Vascular Smooth Muscle Cells Regulates Monocyte Survival and Differentiation Through Distinct Pathways

Cai

Lanting

Natarajan

2004

ATVB

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Objective-Vascular smooth muscle cells (VSMCs) may regulate monocyte functions within atherosclerotic lesions. We investigated the impact of VSMC/monocyte interactions on monocyte apoptosis and scavenger receptor CD36 expression, key events related to monocyte survival and differentiation. Methods and Results-Serum deprivation significantly increased THP-1 and human peripheral blood monocyte apoptosis.However, this was significantly reversed by physical binding to human VSMCs (HVSMCs). On binding to HVSMCs, antiapoptotic kinase Akt and its downstream targets were phosphorylated, and Bcl-2 expression was enhanced.Binding-mediated suppression of apoptosis and Akt phosphorylation were attenuated by a phosphoinositide 3-kinase inhibitor and also by an antibody to vascular cell adhesion molecule-1. CD36 expression was also significantly increased in THP-1 cells and in human peripheral blood monocytes after binding to HVSMCs, and this was mediated by both direct contact and soluble factors. Extracellular signal-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinase phosphorylation was increased in THP-1 cells after HVSMC coculture. Furthermore, an ERK1/2 inhibitor blocked monocyte CD36 upregulation. Contact-dependent CD36 induction and ERK1/2 phosphorylation in monocytes were inhibited by blocking vascular cell adhesion molecule-1 on HVSMC, whereas soluble factor-induced CD36 expression was attenuated by a monocyte chemoattractant protein-1 neutralizing antibody. I n response to atherogenic stimuli, monocytes in circulation adhere and migrate across the endothelium to the intimal space where they differentiate, take up lipid, and form foam cells. The role of vascular endothelial cells in the recruitment of monocytes during early steps of atherosclerosis has been well studied. [1][2][3] However, these initial processes may be reversible and do not cause clinical consequences. 1,2 It is the subsequent prolonged intimal retention of monocyte/macrophage and foam cell formation that are central features of atherogenesis. 1,2 However, the mechanisms by which monocytes/macrophages are retained within the vessel wall, survive, and differentiate to foam cells are not well documented. Once they transmigrate into the subendothelial intimal space, these monocyte functions are regulated mainly by the influence of local factors that are not well characterized. Furthermore, very little is known about the role of intimal vascular smooth muscle cells (VSMCs) in regulating subendothelial monocyte functions. Conclusions-TheseVSMC migration and proliferation are also welldocumented hallmarks of early atherosclerotic lesions. 1,4 Accumulating evidence suggests that interactions between transmigrated monocytes and VSMCs may contribute to monocyte retention and function within the vasculature. First, the potential of VSMCs to interact with monocytes is suggested by the fact that VSMCs express adhesion molecules within atherosclerotic lesions but not in the normal vascular wall. 5 A highly significant association was found between V...

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Section: Discussionmentioning

confidence: 93%

Interaction of Monocytes With Vascular Smooth Muscle Cells Regulates Monocyte Survival and Differentiation Through Distinct Pathways

Cai

Lanting

Natarajan

2004

ATVB

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“…Recently, we reported that mechanical stress activates p38 MAPK and induces cellular hypertrophy through the integrin-focal adhesion kinase (FAK)-Src-Ras pathway [8]. We also reported that activation of integrins by cell adhesion to ECM proteins induces MCP-1 expression in mesangial cells through activation of FAK [7], indicating that integrin activation by mechanical stress and ligand binding can trigger specific activation of intracellular signalling. Integrins and their cytoplasmic tails are involved in forming large complexes of cytoskeletal proteins and signalling molecules upon cell adhesion to ECM called focal adhesions that include FAK and other signal transduction molecules, such as PDGF receptor and ERK1/2 [9], suggesting the collaboration between integrins and growth factor receptors.…”

Section: Introductionmentioning

confidence: 97%

“…RT-PCR for MCP-1 was performed as described [2,7]. Briefly, mRNA was extracted with the QuickPrep mRNA purification kit (Amersham Pharmacia Biotech, Buckinghamshire, UK).…”

Section: Western Blottingmentioning

confidence: 99%

“…Inflammatory cytokines and growth factors, such as platelet-derived growth factor (PDGF) and interleukin-1, can trigger the expression of MCP-1 through activation of several signalling pathways such as extracellular signal-related kinase (ERK)1/2 [2], p38 mitogen-activated protein (MAP) kinase [3], protein kinase C [4], activator protein (AP)-1 [5] and nuclear factor (NF)-kB [6]. We have reported that integrin-mediated activation of intracellular signalling molecules also induces MCP-1 expression in mesangial cells [7], suggesting that abnormal remodelling of ECM observed in many types of glomerular diseases can upregulate MCP-1 expression.…”

Section: Introductionmentioning

confidence: 99%

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Synergistic induction of monocyte chemoattractant protein-1 by integrins and platelet-derived growth factor via focal adhesion kinase in mesangial cells

Kanegae¹,

Tamura²,

Kabashima³

et al. 2005

Nephrology Dialysis Transplantation

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Background. Growth factors, extracellular matrix and its receptor integrins are upregulated in various glomerular diseases. We investigated the mechanism of collaboration between integrins and plateletderived growth factor (PDGF) in focal adhesion kinase (FAK)-and extracellular signal-related kinase (ERK)1/2-mediated signal pathways that lead to monocyte chemoattractant protein (MCP)-1 expression in cultured rat mesangial cells (MCs). Methods. Serum-starved MCs were plated on fibronectin-or polylysine-coated plates with or without PDGF, and examined for phosphorylation of ERK1/2, mitogen-activated protein or ERK kinase (MEK)1/2 and FAK by western blotting, and for expression of MCP-1 mRNA and protein by reverse transcriptionpolymerase chain reaction (RT-PCR) and enzymelinked immunosorbent assay (ELISA), respectively. The effects of dominant-negative FAK on MCP-1 expression were examined. Results. Cell adhesion to fibronectin increased phosphorylation of FAK, MEK1/2 and ERK1/2, and induced MCP-1 mRNA and protein expression. PDGF increased phosphorylation of FAK, MEK1/2 and ERK1/2 even without cell adhesion to fibronectin, and induced MCP-1 mRNA and protein expression. PDGF with integrin activation by fibronectin synergistically increased phosphorylation of FAK, MEK1/2 and ERK1/2, and expression of MCP-1 mRNA and protein. Dominant-negative FAK attenuated fibronectin enhancement of PDGF-induced ERK1/2 phosphorylation and MCP-1 expression, indicating involvement of FAK in this signalling. Conclusions.Our results suggest the cooperative role of integrin and PDGF receptor in activation of the ERK pathway possibly via FAK in MCs. The synergistic activation of integrin and PDGF signalling may play an important role in the progression of glomerular diseases through the induction of MCP-1.

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“…FAK also participates in immune and inflammatory response signaling by regulating cytokine production (8). FAK is important for lipopolysaccharide-induced interleukin-6 (IL-6) secretion by human and murine fibroblasts (9).…”

Section: Focal Adhesion Kinase (Fak)mentioning

confidence: 99%

Tumor Necrosis Factor-α Stimulates Focal Adhesion Kinase Activity Required for Mitogen-activated Kinase-associated Interleukin 6 Expression

Schlaepfer

Hou

Lim

et al. 2007

Journal of Biological Chemistry

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Moreover, analyses of Src؊/؊ , Yes ؊/؊ , and Fyn ؊/؊ fibroblasts showed that Src expression was inhibitory to TNF␣-stimulated IL-6 production. These studies provide evidence for a novel Srcindependent FAK to MAPK signaling pathway regulating IL-6 expression with potential importance to inflammation and tumor progression. Focal adhesion kinase (FAK)2 is best known for its role as an integrin-stimulated protein-tyrosine kinase (1). FAK is recruited to sites of integrin clustering via interactions of its C-terminal domain with integrin-associated proteins such as talin and paxillin. FAK contains a central kinase domain, C-terminal proline-rich regions that serve as binding sites for Src homology 3 (SH3) domain-containing proteins, and an N-terminal band 4.1, ezrin, radixin, moesin homology (FERM) domain that acts to regulate FAK kinase activity through an auto-inhibitory mechanism (2, 3). Integrin clustering promotes FAK activation, results in FAK phosphorylation at Tyr-397 (Tyr(P)-397), promotes Src family protein-tyrosine kinase binding to the FAK Tyr(P)-397 site, and facilitates the formation of the FAK-Src signaling complex that results in the secondary phosphorylation of FAK at Tyr-861 and Tyr-925 (4, 5).

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Integrins induce expression of monocyte chemoattractant protein-1 via focal adhesion kinase in mesangial cells

Abstract: Our results indicate that integrin-mediated cell adhesion to the ECM can induce MCP-1 expression through activation of FAK, and suggest a role for altered ECM deposition in the progression of glomerular diseases by affecting gene expression.

Cited by 22 publications

References 40 publications

Interaction of Monocytes With Vascular Smooth Muscle Cells Regulates Monocyte Survival and Differentiation Through Distinct Pathways

Interaction of Monocytes With Vascular Smooth Muscle Cells Regulates Monocyte Survival and Differentiation Through Distinct Pathways

Synergistic induction of monocyte chemoattractant protein-1 by integrins and platelet-derived growth factor via focal adhesion kinase in mesangial cells

Tumor Necrosis Factor-α Stimulates Focal Adhesion Kinase Activity Required for Mitogen-activated Kinase-associated Interleukin 6 Expression

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