A Novel Role for Nuclear Factor of Activated T Cells in Receptor Tyrosine Kinase and G Protein-coupled Receptor Agonist-induced Vascular Smooth Muscle Cell Motility

Liu, Zhimin; Dronadula, Nagadhara; Rao, Gadiparthi N.

doi:10.1074/jbc.m406917200

Cited by 58 publications

(71 citation statements)

References 39 publications

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“…It was reported that conditional expression of NFATc1 enhances pancreatic ␤-cell proliferation (37). In addition to these observations, work from our laboratory showed that NFATs mediate VSMC growth and migration in response to both RTK and GPCR agonists (17,18). A role for NFATs in the regulation of VSMC growth has also been supported by the findings that forced expression of constitutively active sarco/ endoplasmic reticulum calcium ATPase inhibits VSMC proliferation through inactivation of calcineurin and its target transcription factor NFAT (38).…”

Section: Discussionsupporting

confidence: 64%

“…Previously, we have shown that NFATs play a role in the regulation of VSMC growth and migration (17,18). Towards understanding the mechanisms of NFATs in the regulation of VSMC migration, we have shown that these transcriptional factors mediate interleukin-6 expression as one of the effector molecules in receptor tyrosine kinase (RTK) and G protein-coupled receptor (GPCR) agonist-induced VSMC motility (18). In addition, we have reported the involvement of NFATs in injury-induced neointima formation (19).…”

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confidence: 99%

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Cyclin D1 Is a Bona Fide Target Gene of NFATc1 and Is Sufficient in the Mediation of Injury-induced Vascular Wall Remodeling

Karpurapu

Wang

Quyền

et al. 2010

Journal of Biological Chemistry

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Platelet-derived growth factor BB induced cyclin D1 expression in a time-and nuclear factor of activated T cells (NFAT)-dependent manner in human aortic smooth muscle cells (HASMCs), and blockade of NFATs prevented HASMC DNA synthesis and their cell cycle progression from G 1 to S phase. Selective inhibition of NFATc1 by its small interfering RNA also blocked HASMC proliferation and migration. Characterization of the cyclin D1 promoter revealed the presence of several NFAT binding sites, and the site at nucleotide ؊1333 was found to be sufficient in mediating platelet-derived growth factor BBinduced cyclin D1 promoter-luciferase reporter gene activity. In addition to its role in cell cycle progression, cyclin D1 mediated HASMC migration in an NFATc1-dependent manner. Balloon injury-induced cyclin D1-CDK4 activity requires NFAT activation, and adenovirus-mediated transduction of cyclin D1 was found to be sufficient to overcome the blockade effect of NFATs by VIVIT on balloon injury-induced vascular wall remodeling events, including smooth muscle cell migration from the medial to luminal region, their proliferation in the intimal region, and neointima formation. Together, these results provide more mechanistic evidence for the role of NFATs, particularly NFATc1, in the regulation of HASMC proliferation and migration as well as vascular wall remodeling. NFATc1 could be a potential therapeutic target against the renarrowing of artery after angioplasty.

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Section: Discussionsupporting

confidence: 64%

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confidence: 99%

Cyclin D1 Is a Bona Fide Target Gene of NFATc1 and Is Sufficient in the Mediation of Injury-induced Vascular Wall Remodeling

Karpurapu

Wang

Quyền

et al. 2010

Journal of Biological Chemistry

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“…In RIE/GPRP-R cells, BBSmediated transcriptional induction of the Cox-2 gene is also calcium dependent, requiring activation of components of the AP-1 transcription factor complex, such as Fos/Jun proteins (Guo et al, 2001). Moreover, involvement of Gaq-coupled receptors as the GRP-R in the activation of NFAT and in the induction of NFATdependent genes has been described in a variety of cell types (Boss et al, 1996;Horsley and Pavlath, 2002;Liu et al, 2004). Noticeably, recent reports have proposed that NFAT proteins may play an important role in cancer, having shown a direct involvement of NFATmediated transcriptional regulation of different genes, including Cox-2 (Jauliac et al, 2002;Lara-Pezzi et al, 2002;Saurin et al, 2002;Neal and Clipstone, 2003;Holzmann et al, 2004;Yiu and Toker, 2006).…”

Section: Discussionmentioning

confidence: 99%

Bombesin induces cyclooxygenase-2 expression through the activation of the nuclear factor of activated T cells and enhances cell migration in Caco-2 colon carcinoma cells

et al. 2006

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Cyclooxygenase-2 (Cox-2), the gastrin-release peptide (GRP) and its cognate receptor (GRP-R) are overexpressed in a significant percentage of colorectal carcinomas and are associated with cell growth, invasiveness and tumor progression. However, a molecular link between all of them in adenocarcinomas has not been established. Here, we show that bombesin (BBS), a GRP homolog, stimulates the expression of Cox-2 mRNA and protein in human colon adenocarcinoma Caco-2 cells, resulting in enhanced release of prostaglandin E 2 . These effects were markedly inhibited by the specific BBS antagonist RC-3940-II. BBS promotes the activation of the nuclear factor of activated T cells (NFAT) through a Ca 2 þ /calcineurin (Cn)-linked pathway. Upon BBS stimulation, the NFATc1 isoform translocates into the nucleus with a concomitant increase in NFATc1 binding to two specific recognition sites in the promoter region of the Cox-2 gene. Furthermore, inhibition of Cn activity by the immunosuppressive drug cyclosporin A impaired NFAT activation and diminished Cox-2 expression in BBSstimulated cells. Interestingly, BBS pretreatment strongly enhances the invasive capacity of carcinoma cells, effect which was inhibited by a Cox-2-specific inhibitor. These findings provide the first evidence for the involvement of the Ca 2 þ /Cn/NFAT pathway in BBS-mediated induction of genes involved in colon carcinoma invasiveness such as Cox-2. Oncogene (2007) 26, 958-969.

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“…9,10 IL-6 is produced from many cell types, including vascular smooth muscle cells (VSMCs). It was reported that the IL-6 expression in VSMCs is induced by IL-1, 11 platelet-derived growth factor 12 and Ang II. 13 The induction of IL-6 by Ang II is reported to be dependent on the activation of two transcription factors, cAMP-response element-binding (CREB) protein 13,14 and nuclear factor-kappa B (NF-kB).…”

Section: Introductionmentioning

confidence: 99%

Resveratrol attenuates angiotensin II-induced interleukin-6 expression and perivascular fibrosis

et al. 2009

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Recent studies have shown that resveratrol (3,5,4¢-trihydroxystilbene), a polyphenolic compound found in grapes and red wine, has various beneficial effects on cardiovascular diseases and prolongs the life span of mice fed a high-fat diet. We hypothesized that resveratrol may attenuate vascular inflammatory response induced by angiotensin (Ang) II. We examined the effect of resveratrol on Ang II-induced interleukin (IL)-6 expression in vascular smooth muscle cells (VSMCs). Resveratrol significantly attenuated Ang II-induced IL-6 mRNA expression and IL-6 protein in the supernatant of VSMC in a dose-dependent manner. Resveratrol suppressed the IL-6 gene promoter activity. Resveratrol inhibited the Ang II-induced cAMP-response element-binding protein and nuclear factor-kappa B activity, which are critical for Ang II-induced IL-6 gene activation. An increase in the serum concentration of IL-6 induced by Ang II infusion was attenuated by an oral administration of resveratrol. Resveratrol also inhibited Ang II-induced hypertension and perivascular fibrosis of the heart. Although hydralazine reduced blood pressure level equal to resveratrol, it did not reduce the Ang II-induced IL-6 production and perivascular fibrosis. These data suggest that the inhibition of Ang II-induced vascular inflammation and high blood pressure by resveratrol may contribute, at least in part, to the anti-atherogenic effects of resveratrol.

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A Novel Role for Nuclear Factor of Activated T Cells in Receptor Tyrosine Kinase and G Protein-coupled Receptor Agonist-induced Vascular Smooth Muscle Cell Motility

Cited by 58 publications

References 39 publications

Cyclin D1 Is a Bona Fide Target Gene of NFATc1 and Is Sufficient in the Mediation of Injury-induced Vascular Wall Remodeling

Cyclin D1 Is a Bona Fide Target Gene of NFATc1 and Is Sufficient in the Mediation of Injury-induced Vascular Wall Remodeling

Bombesin induces cyclooxygenase-2 expression through the activation of the nuclear factor of activated T cells and enhances cell migration in Caco-2 colon carcinoma cells

Resveratrol attenuates angiotensin II-induced interleukin-6 expression and perivascular fibrosis

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