Sirolimus inhibits platelet-derived growth factor-induced collagen synthesis in rat vascular smooth muscle cells

J. Park, H. Ha, H. J. Ahn, S. W. Kang, Y. S. Kim, J. Y. Seo, M. S. Kim

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Vascular smooth muscle cell (VSMC) proliferation and extracellular matrix (ECM) accumulation play key roles in the development and the progression of vascular remodeling such as transplant arteriosclerosis and restenosis. The present study examined the effects of sirolimus (SRL) on platelet-derived growth factor (PDGF)-induced fibronectin secretion, collagen synthesis, and the related signaling pathways including reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPK) in rat VSMCs. Primary rat VSMCs were isolated from male Sprague-Dawley rats. Growth arrested, synchronized cells were treated with various concentrations of SRL before the addition of PDGF at 10 ng/mL. Proliferating cell nuclear antigen expression, fibronectin secretion, and the activation of extracellular signal-regulated protein kinase (ERK) and p38 MAPK were assessed by Western blot analysis, collagen synthesis by [ 3H]-proline incorporation, and cellular ROS by flow cytometry. PDGF (10 ng/mL) increased VSMC proliferation by 1.7-fold, fibronectin secretion by 1.5-fold, collagen synthesis by 2.1-fold, cellular ROS by 1.6-fold, and activation of ERK and p38 MAPK by 3.3- and 3.9-fold compared to controls. SRL above 1 nmol/L inhibited PDGF-induced VSMC proliferation and collagen synthesis but not PDGF-induced fibronectin secretion, cellular ROS, and activation of ERK and p38 MAPK. These data demonstrated that PDGF increased ECM synthesis as well as proliferation through cellular ROS and subsequent MAPK activation and that SRL inhibited PDGF-induced VSMC proliferation and collagen synthesis in a cellular ROS- and MAPK activation-independent way.

Original languageEnglish
Pages (from-to)3459-3462
Number of pages4
JournalTransplantation Proceedings
Volume37
Issue number8
DOIs
Publication statusPublished - 2005 Oct 1

Fingerprint

Platelet-Derived Growth Factor
Sirolimus
Vascular Smooth Muscle
Smooth Muscle Myocytes
Collagen
Reactive Oxygen Species
Fibronectins
Cell Proliferation
p38 Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinases
Extracellular Matrix
Arteriosclerosis
Extracellular Signal-Regulated MAP Kinases
Proliferating Cell Nuclear Antigen
Proline
Protein Kinases
Sprague Dawley Rats
Flow Cytometry
Western Blotting
Transplants

All Science Journal Classification (ASJC) codes

  • Surgery
  • Transplantation

Cite this

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title = "Sirolimus inhibits platelet-derived growth factor-induced collagen synthesis in rat vascular smooth muscle cells",
abstract = "Vascular smooth muscle cell (VSMC) proliferation and extracellular matrix (ECM) accumulation play key roles in the development and the progression of vascular remodeling such as transplant arteriosclerosis and restenosis. The present study examined the effects of sirolimus (SRL) on platelet-derived growth factor (PDGF)-induced fibronectin secretion, collagen synthesis, and the related signaling pathways including reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPK) in rat VSMCs. Primary rat VSMCs were isolated from male Sprague-Dawley rats. Growth arrested, synchronized cells were treated with various concentrations of SRL before the addition of PDGF at 10 ng/mL. Proliferating cell nuclear antigen expression, fibronectin secretion, and the activation of extracellular signal-regulated protein kinase (ERK) and p38 MAPK were assessed by Western blot analysis, collagen synthesis by [ 3H]-proline incorporation, and cellular ROS by flow cytometry. PDGF (10 ng/mL) increased VSMC proliferation by 1.7-fold, fibronectin secretion by 1.5-fold, collagen synthesis by 2.1-fold, cellular ROS by 1.6-fold, and activation of ERK and p38 MAPK by 3.3- and 3.9-fold compared to controls. SRL above 1 nmol/L inhibited PDGF-induced VSMC proliferation and collagen synthesis but not PDGF-induced fibronectin secretion, cellular ROS, and activation of ERK and p38 MAPK. These data demonstrated that PDGF increased ECM synthesis as well as proliferation through cellular ROS and subsequent MAPK activation and that SRL inhibited PDGF-induced VSMC proliferation and collagen synthesis in a cellular ROS- and MAPK activation-independent way.",
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Sirolimus inhibits platelet-derived growth factor-induced collagen synthesis in rat vascular smooth muscle cells. / Park, J.; Ha, H.; Ahn, H. J.; Kang, S. W.; Kim, Y. S.; Seo, J. Y.; Kim, M. S.

In: Transplantation Proceedings, Vol. 37, No. 8, 01.10.2005, p. 3459-3462.

Research output: Contribution to journalArticle

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AU - Park, J.

AU - Ha, H.

AU - Ahn, H. J.

AU - Kang, S. W.

AU - Kim, Y. S.

AU - Seo, J. Y.

AU - Kim, M. S.

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