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Lysophosphatidic acid regulates the proliferation and migration of olfactory ensheathing cells in vitro
Author(s) -
Yan Henglin,
Lu Dongchen,
Rivkees Scott A.
Publication year - 2003
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.10265
Subject(s) - lysophosphatidic acid , microbiology and biotechnology , olfactory ensheathing glia , biology , rho kinase inhibitor , actin cytoskeleton , wortmannin , cell migration , rho associated protein kinase , focal adhesion , signal transduction , cytoskeleton , neuroscience , pi3k/akt/mtor pathway , receptor , cell , olfactory bulb , biochemistry , central nervous system
Olfactory ensheathing cells (OECs) are a unique type of macroglia with axonal growth‐promoting properties. However, our understanding of the factors that regulate OECs is at early stages. Lysophosphatidic acid (LPA) is a lipid that influences diverse functions in the nervous system. Recent studies suggest that glial cells, including astrocytes and Schwann cells, are important targets of LPA. However, the influences of LPA on OECs are not known. To address if LPA can influence OECs, we examined effects of LPA on the proliferation and migration of OECs and intracellular effector events. Initially, we observed that OECs expressed the genes for LPA 1 , LPA 2 , and LPA 3 receptors. When OECs were treated with LPA, we observed stimulated proliferation and migration of OECs. Treatment of OECs with LPA also induced actin cytoskeleton reorganization and focal adhesion assembly. These effects of LPA were blocked by treatment with C3 exoenzyme or Y‐27632, which inhibit Rho‐GTPase and Rho‐associated kinase, respectively. Effects of LPA on OEC proliferation were blocked by the MEK inhibitors PD098059 and U0126 and by the phosphotidylinositol 3‐kinase (PI 3‐K) inhibitors LY0294002 and wortmannin. These results show that LPA acts via Rho‐GTPase, MAPK, and PI 3‐K signaling cascades to influence OEC proliferation, migration, and cytoskeleton assembly. © 2003 Wiley‐Liss, Inc.