Cyclin D1 is a Bona fide target gene of NFATc1 and is sufficient in the mediation of injury-induced vascular wall remodeling

Manjula Karpurapu, Dong Wang, Dong Van Quyen, Tae Kang Kim, Venkatesh Kundumani-Sridharan, Srinidhi Pulusani, Rao Gadiparthi

Research output: Contribution to journalArticle

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Abstract

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 G1 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 BB-induced 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.

Original languageEnglish (US)
Pages (from-to)3510-3523
Number of pages14
JournalJournal of Biological Chemistry
Volume285
Issue number5
DOIs
StatePublished - Jan 29 2010

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Cyclin D1
Smooth Muscle Myocytes
Muscle
Genes
NFATC Transcription Factors
Cell Movement
Wounds and Injuries
Cells
Balloons
Cell proliferation
Cell Cycle
Cell Proliferation
Tunica Intima
Neointima
Luciferases
S Phase
Reporter Genes
Angioplasty
Adenoviridae
Small Interfering RNA

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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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, Manjula; Wang, Dong; Van Quyen, Dong; Kim, Tae Kang; Kundumani-Sridharan, Venkatesh; Pulusani, Srinidhi; Gadiparthi, Rao.

In: Journal of Biological Chemistry, Vol. 285, No. 5, 29.01.2010, p. 3510-3523.

Research output: Contribution to journalArticle

Karpurapu, Manjula ; Wang, Dong ; Van Quyen, Dong ; Kim, Tae Kang ; Kundumani-Sridharan, Venkatesh ; Pulusani, Srinidhi ; Gadiparthi, Rao. / Cyclin D1 is a Bona fide target gene of NFATc1 and is sufficient in the mediation of injury-induced vascular wall remodeling. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 5. pp. 3510-3523.
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