Eicosapentaenoic acid inhibits PDGF-induced mitogenesis and cyclin D1 expression via TGF-β in mesangial cells

Mariko Hida, Hisayo Fujita, Kenji Ishikura, Sayu Omori, Makiko Hoshiya, Midori Awazu

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Eicosapentaenoic acid (EPA), an ω-3 polyunsaturated fatty acid derived from fish oil, is efficacious in glomerular diseases where mesangial proliferation is a key event. We examined the mechanisms of action of EPA on platelet-derived growth factor (PDGF)-stimulated rat mesangial cell mitogenesis. EPA dose-dependently inhibited PDGF-stimulated [3H]-thymidine incorporation. PDGF-induced PDGF receptor autophosphorylation, an initial event for PDGF signaling, was not affected by 2 μg/ml EPA. Similarly, PDGF-stimulated activation of extracellular signal-regulated kinase (ERK) was not altered. On the other hand, EPA inhibited cyclin-dependent kinase 4 (CDK4) activation and cyclin D1 protein induction, a critical step for G1/S progression. TGF-β secretion assessed by ELISA and bioassay was increased by EPA at 18 h. Coincubation with anti-TGF-β antibody inhibited the EPA-induced suppression of [3H]-thymidine incorporation and cyclin D1 expression. SB203580, an inhibitor of p38, a downstream kinase of TGF-β, did not affect EPA's growth inhibitory effect. These results demonstrate that EPA inhibits PDGF-stimulated mesangial cell mitogenesis and cyclin D1 expression via TGF-β.

Original languageEnglish
Pages (from-to)293-300
Number of pages8
JournalJournal of Cellular Physiology
Volume196
Issue number2
DOIs
Publication statusPublished - 2003 Aug 1

Fingerprint

Eicosapentaenoic Acid
Mesangial Cells
Cyclin D1
Platelet-Derived Growth Factor
Thymidine
Chemical activation
Cyclin-Dependent Kinase 4
Platelet-Derived Growth Factor Receptors
Fish Oils
Bioassay
Extracellular Signal-Regulated MAP Kinases
Unsaturated Fatty Acids
Biological Assay
Rats
Anti-Idiotypic Antibodies
Phosphotransferases
Enzyme-Linked Immunosorbent Assay
Antibodies
Growth

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Eicosapentaenoic acid inhibits PDGF-induced mitogenesis and cyclin D1 expression via TGF-β in mesangial cells. / Hida, Mariko; Fujita, Hisayo; Ishikura, Kenji; Omori, Sayu; Hoshiya, Makiko; Awazu, Midori.

In: Journal of Cellular Physiology, Vol. 196, No. 2, 01.08.2003, p. 293-300.

Research output: Contribution to journalArticle

Hida, Mariko ; Fujita, Hisayo ; Ishikura, Kenji ; Omori, Sayu ; Hoshiya, Makiko ; Awazu, Midori. / Eicosapentaenoic acid inhibits PDGF-induced mitogenesis and cyclin D1 expression via TGF-β in mesangial cells. In: Journal of Cellular Physiology. 2003 ; Vol. 196, No. 2. pp. 293-300.
@article{d550ad928d884ef0b5d0fbc5d88676cc,
title = "Eicosapentaenoic acid inhibits PDGF-induced mitogenesis and cyclin D1 expression via TGF-β in mesangial cells",
abstract = "Eicosapentaenoic acid (EPA), an ω-3 polyunsaturated fatty acid derived from fish oil, is efficacious in glomerular diseases where mesangial proliferation is a key event. We examined the mechanisms of action of EPA on platelet-derived growth factor (PDGF)-stimulated rat mesangial cell mitogenesis. EPA dose-dependently inhibited PDGF-stimulated [3H]-thymidine incorporation. PDGF-induced PDGF receptor autophosphorylation, an initial event for PDGF signaling, was not affected by 2 μg/ml EPA. Similarly, PDGF-stimulated activation of extracellular signal-regulated kinase (ERK) was not altered. On the other hand, EPA inhibited cyclin-dependent kinase 4 (CDK4) activation and cyclin D1 protein induction, a critical step for G1/S progression. TGF-β secretion assessed by ELISA and bioassay was increased by EPA at 18 h. Coincubation with anti-TGF-β antibody inhibited the EPA-induced suppression of [3H]-thymidine incorporation and cyclin D1 expression. SB203580, an inhibitor of p38, a downstream kinase of TGF-β, did not affect EPA's growth inhibitory effect. These results demonstrate that EPA inhibits PDGF-stimulated mesangial cell mitogenesis and cyclin D1 expression via TGF-β.",
author = "Mariko Hida and Hisayo Fujita and Kenji Ishikura and Sayu Omori and Makiko Hoshiya and Midori Awazu",
year = "2003",
month = "8",
day = "1",
doi = "10.1002/jcp.10298",
language = "English",
volume = "196",
pages = "293--300",
journal = "Journal of Cellular Physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",
number = "2",

}

TY - JOUR

T1 - Eicosapentaenoic acid inhibits PDGF-induced mitogenesis and cyclin D1 expression via TGF-β in mesangial cells

AU - Hida, Mariko

AU - Fujita, Hisayo

AU - Ishikura, Kenji

AU - Omori, Sayu

AU - Hoshiya, Makiko

AU - Awazu, Midori

PY - 2003/8/1

Y1 - 2003/8/1

N2 - Eicosapentaenoic acid (EPA), an ω-3 polyunsaturated fatty acid derived from fish oil, is efficacious in glomerular diseases where mesangial proliferation is a key event. We examined the mechanisms of action of EPA on platelet-derived growth factor (PDGF)-stimulated rat mesangial cell mitogenesis. EPA dose-dependently inhibited PDGF-stimulated [3H]-thymidine incorporation. PDGF-induced PDGF receptor autophosphorylation, an initial event for PDGF signaling, was not affected by 2 μg/ml EPA. Similarly, PDGF-stimulated activation of extracellular signal-regulated kinase (ERK) was not altered. On the other hand, EPA inhibited cyclin-dependent kinase 4 (CDK4) activation and cyclin D1 protein induction, a critical step for G1/S progression. TGF-β secretion assessed by ELISA and bioassay was increased by EPA at 18 h. Coincubation with anti-TGF-β antibody inhibited the EPA-induced suppression of [3H]-thymidine incorporation and cyclin D1 expression. SB203580, an inhibitor of p38, a downstream kinase of TGF-β, did not affect EPA's growth inhibitory effect. These results demonstrate that EPA inhibits PDGF-stimulated mesangial cell mitogenesis and cyclin D1 expression via TGF-β.

AB - Eicosapentaenoic acid (EPA), an ω-3 polyunsaturated fatty acid derived from fish oil, is efficacious in glomerular diseases where mesangial proliferation is a key event. We examined the mechanisms of action of EPA on platelet-derived growth factor (PDGF)-stimulated rat mesangial cell mitogenesis. EPA dose-dependently inhibited PDGF-stimulated [3H]-thymidine incorporation. PDGF-induced PDGF receptor autophosphorylation, an initial event for PDGF signaling, was not affected by 2 μg/ml EPA. Similarly, PDGF-stimulated activation of extracellular signal-regulated kinase (ERK) was not altered. On the other hand, EPA inhibited cyclin-dependent kinase 4 (CDK4) activation and cyclin D1 protein induction, a critical step for G1/S progression. TGF-β secretion assessed by ELISA and bioassay was increased by EPA at 18 h. Coincubation with anti-TGF-β antibody inhibited the EPA-induced suppression of [3H]-thymidine incorporation and cyclin D1 expression. SB203580, an inhibitor of p38, a downstream kinase of TGF-β, did not affect EPA's growth inhibitory effect. These results demonstrate that EPA inhibits PDGF-stimulated mesangial cell mitogenesis and cyclin D1 expression via TGF-β.

UR - http://www.scopus.com/inward/record.url?scp=0038121793&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038121793&partnerID=8YFLogxK

U2 - 10.1002/jcp.10298

DO - 10.1002/jcp.10298

M3 - Article

C2 - 12811822

AN - SCOPUS:0038121793

VL - 196

SP - 293

EP - 300

JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

SN - 0021-9541

IS - 2

ER -