C-reactive protein (CRP) increases VEGF-A expression in monocytic cells via a PI3-kinase and ERK 1/2 signaling dependent pathway

Bello, Gaëlle; Cailotto, F.; Hanriot, Didier; Kolopp‐Sarda, Marie‐Nathalie; Latger‐Cannard, Véronique; Heß, K.; Zannad, Faı̈ez; Longrois, Dan; Ropars, Armelle

doi:10.1016/j.atherosclerosis.2007.12.046

Cited by 36 publications

(28 citation statements)

References 32 publications

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“…Moreover, ROS inhibitor NAC decreased ERK1/2 phosphorylation and RAGE expression, suggesting ROS is upstream of ERK1/2 and RAGE. This finding is in agreement with previous studies showing that CRP activates ERK1/2 in endothelial cells [12] , macrophages [24] and cardiomyocytes [25] . Meanwhile, we used a selective ERK1/2 inhibitor PD98059 to determine whether ERK1/2 is involved in CRP-induced RAGE expression.…”

Section: Discussionsupporting

confidence: 83%

C-reactive protein stimulates RAGE expression in human coronary artery endothelial cells in vitro via ROS generation and ERK/NF-κB activation

et al. 2015

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Aim:The receptor for advanced glycation end-products (RAGE) plays an important role in development of atherosclerosis, and C-reactive protein (CRP) has been found to stimulate its expression in endothelial cells. In this study we investigated how CRP regulated the expression of RAGE in human coronary artery endothelial cells (HCAECs). Methods: HCAECs were treated in vitro with CRP (50 μg/mL) in combination with a variety of inhibitors. ROS generation was determined by immunocytochemistry and flow cytometry. The RAGE expression and phosphorylation of relevant signaling proteins were measured using Western blot analyses. Results: CRP stimulated the expression of RAGE in the cells, accompanied by markedly increased ROS generation, phosphorylation of ERK1/2 and NF-κB p65, as well as translocation of NF-κB p65 to the nuclei. CRP also stimulated phosphorylation of JNK and p38 MAPK. Pretreatment of the cells with the ROS scavenger N-acetyl-L-cysteine, ERK inhibitor PD98059 or NF-κB inhibitor PDTC blocked CRP-stimulated RAGE expression, but pretreatment with the NADPH oxidase inhibitor DPI, JNK inhibitor SP600125 or p38 MAPK inhibitor SB203580 did not significantly alter CRP-stimulated RAGE expression. Conclusion: CRP stimulates RAGE expression in HCAECs in vitro via ROS generation and activation of the ERK/NF-κB signaling pathway.

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Section: Discussionsupporting

confidence: 83%

C-reactive protein stimulates RAGE expression in human coronary artery endothelial cells in vitro via ROS generation and ERK/NF-κB activation

et al. 2015

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“…It has been reported that CRP is capable of signaling through ERK1/2 to induce VEGF by inflammatory macrophages and MMP-10 by cardiomyocytes. 24, 25 We have also demonstrated that activation of ERK12/p38 MAP kinases in response to angiotensin II or advanced glycation-end products is able to induce Smad3 signaling. 26–28 The present study adds to these findings and suggests that CRP induces rapid Smad3 activation in TEC via a CD32-ERK1/2 and p38 MAP kinase-crosstalk pathway, since blockade of CRP signaling with a neutralizing CD32 antibody or ERK1/2 and p38 signaling with inhibitors is capable of inhibiting CRP-induced phosphorylation of Smad3.…”

Section: Discussionmentioning

confidence: 76%

C-reactive protein promotes acute kidney injury via Smad3-dependent inhibition of CDK2/cyclin E

Lai

Tang

Huang

et al. 2016

Kidney International

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Previous studies have shown that acute kidney injury (AKI) is exacerbated in C-reactive protein transgenic mice (CRP Tg) and alleviated in Smad3 knockout mice (Smad3 KO). The present study used CRP Tg, Smad3 KO, and CRP Tg/Smad3 KO mice to investigate the signaling mechanisms by which CRP promotes AKI. As previously reported, we found that the elevation of serum creatinine and the extent of tubular epithelial cell (TEC) necrosis following ischemia-reperfusion injury (IRI) induced AKI was greater for CRP Tg than wild type (Wt). In contrast in Smad3 KO mice, whether CRP Wt or CRP Tg, these responses were blunted. Exacerbation of AKI in CRP Tg was associated with increased TGF-β/Smad3 signaling, i.e. increased expression of the cyclin kinase inhibitor p27, suppression of phosphorylated CDK2, and decreased expression of cyclin E. Concomitantly, TEC proliferation was arrested at the G1 phase in CRP Tg, as evidenced by fewer BrdU+ and PCNA+ cells. On the other hand protection from AKI in Smad3 KO mice was associated with decreased expression of p27 and promotion of CDK2/cyclin E-dependent G1/S transition of TECs. In vitro studies using human TEC showed that (i) CRP activates Smad3 via both TGF-β-dependent and ERK/MAPK crosstalk mechanisms, (ii) Smad3 binds directly to p27, and (iii) blockade of Smad3 or the Fc receptor CD32 prevents CRP-induced p27-dependent G1 cell cycle arrest. In vivo, treatment of CRP Tg with a Smad3 inhibitor improved AKI outcomes. In their sum these data suggest that in CRP Tg mice undergoing AKI, impaired TEC regeneration is likely the result of CD32-Smad3-p27 driven inhibition of the CDK2/cyclin E complex. Targeting Smad3 may offer a new treatment approach for AKI.

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“…1 C-reactive protein (CRP) is not merely a validated inflammatory biomarker but a modulator that drives a direct proinflammatory effect on the different vascular cells implicated in atherogenesis. 2,3 It has been reported that CRP upregulates the expression of vascular endothelial growth factor-A (VEGF-A) and inducible nitric oxide synthase (iNOS) in the vascular cells 4,5 and inhibits the activation of glucocorticoid receptor (GR) in rat vascular smooth muscle cells (VSMCs). 6 On account of the proinflammatory effect of CRP on the vascular cells, it is an important molecule that links inflammation to atherogenesis.…”

Section: Introductionmentioning

confidence: 99%

Rosiglitazone Regulates C-reactive Protein–induced Inflammatory Responses Via Glucocorticoid Receptor–mediated Inhibition of p38 Mitogen-activated Protein Kinase–Toll-like Receptor 4 Signal Pathway in Vascular Smooth Muscle Cells

Liu¹,

Liu²,

Ji³

et al. 2011

Journal of Cardiovascular Pharmacology

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C-reactive protein (CRP) activates toll-like receptor 4 (TLR4) to initiate inflammatory response involved in the pathogenesis of atherosclerosis through mitogen-activated protein kinase (MAPK) signal pathways. Rosiglitazone, a synthetic peroxisome proliferator-activated receptor γ (PPARγ) agonist, is considered to be an important inhibitor of the inflammatory response. The present study was to explore the effect of rosiglitazone on the CRP-induced inflammatory responses and the related signal pathway in vascular smooth muscle cells (VSMCs). The results showed that rosiglitazone reduced the expressions of proinflammatory cytokines, such as vascular endothelial growth factor-A and inducible nitric oxide synthase, and enhanced the expression or activation of anti-inflammatory transcription factors including PPARγ and glucocorticoid receptor (GR) in VSMCs in response to CRP. The further investigations indicated that rosiglitazone inhibited CRP-induced TLR4 expression and p38 MAPK phosphorylation in VSMCs, and TLR4 knockdown potentiated the inhibitory effects of rosiglitazone on vascular endothelial growth factor-A and inducible nitric oxide synthase expressions. In addition, GR antagonist RU486 but not PPARγ inhibitor GW9662 remarkably weakened the inhibitory effects of rosiglitazone on CRP-induced TLR4 expression and p38 phosphorylation in VSMCs. But GW9662 did not affect rosiglitazone-induced GR phosphorylation. These suggest that rosiglitazone exerts its anti-inflammatory effect through activating GR and subsequently inhibiting p38 MAPK-TLR4 signaling pathway in CRP-stimulated VSMCs.

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C-reactive protein (CRP) increases VEGF-A expression in monocytic cells via a PI3-kinase and ERK 1/2 signaling dependent pathway

Cited by 36 publications

References 32 publications

C-reactive protein stimulates RAGE expression in human coronary artery endothelial cells in vitro via ROS generation and ERK/NF-κB activation

C-reactive protein stimulates RAGE expression in human coronary artery endothelial cells in vitro via ROS generation and ERK/NF-κB activation

C-reactive protein promotes acute kidney injury via Smad3-dependent inhibition of CDK2/cyclin E

Rosiglitazone Regulates C-reactive Protein–induced Inflammatory Responses Via Glucocorticoid Receptor–mediated Inhibition of p38 Mitogen-activated Protein Kinase–Toll-like Receptor 4 Signal Pathway in Vascular Smooth Muscle Cells

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