New Modes of GPCR Signalling

Autotaxin Signaling via Lysophosphatidic Acid Receptors Contributes to
LPC-Induced Vascular Smooth Muscle Cell Proliferation and Migration
Bao liang, Zhao Gui-jun, Zhang qian,Yang wen-hua, Yang De-zhi, Li Ying-hui,Alatan
Gaole*
(Department of Biochestry and Molecular Biology ,College ofLife Sciences,Inner
Mongolia University,Hohhot,010021)
Background: Lysophosphatidylcholine (LPC) is a major bioactive phospholipid
component of oxidized low-density lipoprotein (Ox-LDL) and is implicated as a critical
factor in the atherogenic activity of Ox-LDL. LPC is believed to play an important role
in atherosclerosis and inflammatory diseases by altering various functions in a number
of cell-types. We have examined that LPC stimulated the proliferation and migratory
responses of cultured human vascular smooth muscle cells(VSMC),and these actions
were inhibited by Ki16425,a receptor antagonist for the ATX enzymatic product
lysophosphatidic acid (LPA) . We also find that ATX were strongly expressed in the
cells. However, the ATX product mediating the increase in cellular proliferation and
motility remain to be identified. Here,we reported that ATX expressed in the cells
contributes to Lpc-induced VSMC Proliferation and migration .Results: LPC and LPA
stimulated hVSMCs proliferation and migration in a PTX-sensitive manner. These
actions were suppressed by using SiRNA sepecific to ATX and LPA1 receptor,Ki16425.
Furthermore, The LPC- and LPA-induced proliferation of hVSMCs was markedly
inhibited by a potent calcineurin inhibitor cyclosporine A and PD98059,a ERK inhibitor.
Instead, an epidermal growth factor (EGF) receptor tyrosine kinase inhibitor and P38
inhibitor markedly suppressed the migration response to LPC and LPA without having
any significant effect on proliferation of VSMC. .Conclusion: The LPC-induced
stimulation of proliferation in VSMC is mediated by the ATX enzymatic product LPA
through LPA1receptors / Gi/o-proteins/ ERK- MAP kinase /Ca 2+ /calcineurin pathways .
The migration response to LPC and LPA are mediated by the ATX enzymatic product
LPA through LPA1-receptors / Gi/o-proteins/ P38- MAP kinase signaling pathway and
also mediated by transactivation of EGF receptor pathways .
Key words: Autotaxin, Lysophosphatidylcholine, Vascular smooth muscle
cells(VSMC), LPA-receptors signaling pathway
Acknowledge: Supported by the National Science Foundation of China (Grant No.
30760052), was also supported in part by Fostering Talents in Basic Research of the
National Natural Science Foundation of China (Grant No.J0730648 ).
Author*: Alatan gaole, PhD, Professer , Department of Biochemstry and Molecular
Biology , College of Life Sciences , Inner Mongolia University. Adress:No.235,West
University Street, Hohhot, Inner Mongolia, 010021,Tel:0471-4993197, E-mail:
bigaole@imu.edu.cn