Eicosapentaenoic acid inhibits PDGF-induced mitogenesis and cyclin D1 expression via TGF-β in mesangial cells
✍ Scribed by Mariko Hida; Hisayo Fujita; Kenji Ishikura; Sayu Omori; Makiko Hoshiya; Midori Awazu
- Publisher
- John Wiley and Sons
- Year
- 2003
- Tongue
- English
- Weight
- 215 KB
- Volume
- 196
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
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 [^3^H]‐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 [^3^H]‐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. J. Cell. Physiol. 196: 293–300, 2003. © 2003 Wiley‐Liss, Inc.