Signaling pathways involved in DNA synthesis and migration in response to lysophosphatidic acid and low-density lipoprotein in coronary artery smooth muscle cells.
Low-density lipoprotein (LDL) and lysophosphatidic acid (LPA), one of the lipid components of lipoprotein, induced the DNA synthesis of coronary artery smooth muscle cells (CASMCs). The LDL- and LPA-induced DNA synthesis was markedly inhibited by the LPA receptor antagonist Ki16425, pertussis toxin, small interfering RNAs targeted for LPA1 receptors, and a potent calcineurin inhibitor cyclosporine A. It has been reported that LDL and LPA induced a migration response in a manner sensitive to Ki16425, pertussis toxin, and a LPA1 receptor-specific small interfering RNA. However, cyclosporine A was ineffective in inhibiting the migration response. Instead, an epidermal growth factor (EGF) receptor tyrosine kinase inhibitor markedly suppressed the migration response to LDL and LPA without having any significant effect on DNA synthesis. Thus, the LDL-induced stimulation of DNA synthesis and migration in CASMCs is mediated by its component LPA through LPA1 receptors and G(i/o)-proteins. Ca2+/calcineurin pathways and transactivation of EGF receptors mediate LPA1-receptor-induced DNA synthesis and migration, respectively.
Komachi
Mayumi
M
Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showo-machi, Maebashi 371-8512, Japan.
Damirin
Alatangaole
A
Malchinkhuu
Enkhzol
E
Mogi
Chihiro
C
Tobo
Masayuki
M
Ohta
Hideo
H
Sato
Koichi
K
Tomura
Hideaki
H
Okajima
Fumikazu
F
D019703:Calcineurin / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000378:metabolism* / Q000502:physiology*; D004247:DNA / Q000096:biosynthesis*; D066246:ErbB Receptors / Q000502:physiology; D006801:Humans; D008077:Lipoproteins, LDL / Q000502:physiology*; D008246:Lysophospholipids / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000502:physiology*; D049368:Receptors, Lysophosphatidic Acid / Q000819:agonists; D015398:Signal Transduction / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology
D008077:Lipoproteins, LDL; D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; D004247:DNA; D066246:ErbB Receptors; D019703:Calcineurin; C032881:lysophosphatidic acid