Novel role for STAT-5B in the regulation of Hsp27-FGF-2 axis facilitating thrombin-induced vascular smooth muscle cell growth and motility

Huiqing Cao, Nagadhara Dronadula, Farhan Rizvi, Quanyi Li, Kalyan Srivastava, William T. Gerthoffer, Rao Gadiparthi

Research output: Contribution to journalArticle

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Abstract

Previously, we have demonstrated that STAT-3 plays a role in thrombin-induced VSMC motility. To learn more about the role of STATs in the mitogenic and chemotactic signaling events of thrombin, here we have studied the role of STAT-5. Thrombin activated STAT-5 as measured by its tyrosine phosphorylation, DNA binding, and reporter gene activity. Inhibition of STAT-5B, but not STAT-5A, by adenovirus-mediated expression of its respective dominant-negative mutants suppressed thrombin-induced VSMC growth and motility. Thrombin induced the expression of Hsp27 and FGF-2 in a time- and STAT-5B-dependent manner in VSMC. In addition, small interfering RNA-directed depletion of Hsp27 levels or adenovirus-mediated expression of its dominant-negative mutant attenuated thrombin-induced FGF-2 expression, growth, and motility of VSMC. An increased association of STAT-5B with STAT-3 occurred in response to thrombin and adenovirus-mediated expression of dnSTAT-3 suppressed thrombin-induced Hsp27 and FGF-2 induction, DNA synthesis and motility in VSMC. Together, these results indicate that thrombin-induced VSMC growth and motility require STAT-5B/STAT-3-dependent expression of Hsp27 and FGF-2. These observations also suggest that STAT-5B/STAT-3/Hsp27/FGF-2 signaling via its involvement in the regulation of VSMC growth and motility may play an important role in the pathogenesis of vascular diseases such as restenosis after angioplasty.

Original languageEnglish (US)
Pages (from-to)913-922
Number of pages10
JournalCirculation research
Volume98
Issue number7
DOIs
StatePublished - Apr 1 2006

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Fibroblast Growth Factor 2
Vascular Smooth Muscle
Thrombin
Smooth Muscle Myocytes
Cell Movement
Growth
Adenoviridae
DNA
Vascular Diseases
Reporter Genes
Angioplasty
Small Interfering RNA
Tyrosine
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine

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Novel role for STAT-5B in the regulation of Hsp27-FGF-2 axis facilitating thrombin-induced vascular smooth muscle cell growth and motility. / Cao, Huiqing; Dronadula, Nagadhara; Rizvi, Farhan; Li, Quanyi; Srivastava, Kalyan; Gerthoffer, William T.; Gadiparthi, Rao.

In: Circulation research, Vol. 98, No. 7, 01.04.2006, p. 913-922.

Research output: Contribution to journalArticle

Cao, Huiqing ; Dronadula, Nagadhara ; Rizvi, Farhan ; Li, Quanyi ; Srivastava, Kalyan ; Gerthoffer, William T. ; Gadiparthi, Rao. / Novel role for STAT-5B in the regulation of Hsp27-FGF-2 axis facilitating thrombin-induced vascular smooth muscle cell growth and motility. In: Circulation research. 2006 ; Vol. 98, No. 7. pp. 913-922.
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AU - Rizvi, Farhan

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AU - Gerthoffer, William T.

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AB - Previously, we have demonstrated that STAT-3 plays a role in thrombin-induced VSMC motility. To learn more about the role of STATs in the mitogenic and chemotactic signaling events of thrombin, here we have studied the role of STAT-5. Thrombin activated STAT-5 as measured by its tyrosine phosphorylation, DNA binding, and reporter gene activity. Inhibition of STAT-5B, but not STAT-5A, by adenovirus-mediated expression of its respective dominant-negative mutants suppressed thrombin-induced VSMC growth and motility. Thrombin induced the expression of Hsp27 and FGF-2 in a time- and STAT-5B-dependent manner in VSMC. In addition, small interfering RNA-directed depletion of Hsp27 levels or adenovirus-mediated expression of its dominant-negative mutant attenuated thrombin-induced FGF-2 expression, growth, and motility of VSMC. An increased association of STAT-5B with STAT-3 occurred in response to thrombin and adenovirus-mediated expression of dnSTAT-3 suppressed thrombin-induced Hsp27 and FGF-2 induction, DNA synthesis and motility in VSMC. Together, these results indicate that thrombin-induced VSMC growth and motility require STAT-5B/STAT-3-dependent expression of Hsp27 and FGF-2. These observations also suggest that STAT-5B/STAT-3/Hsp27/FGF-2 signaling via its involvement in the regulation of VSMC growth and motility may play an important role in the pathogenesis of vascular diseases such as restenosis after angioplasty.

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