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Eicosapentaenoic acid inhibits PDGF‐induced mitogenesis and cyclin D1 expression via TGF‐β in mesangial cells
Author(s) -
Hida Mariko,
Fujita Hisayo,
Ishikura Kenji,
Omori Sayu,
Hoshiya Makiko,
Awazu Midori
Publication year - 2003
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.10298
Subject(s) - platelet derived growth factor receptor , cyclin d1 , mesangial cell , biology , cyclin d , cyclin dependent kinase , platelet derived growth factor , cell growth , transforming growth factor , growth factor , endocrinology , kinase , mapk/erk pathway , medicine , microbiology and biotechnology , cancer research , cell cycle , biochemistry , receptor , kidney , cell
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.