| First Author | Kim J | Year | 2006 |
| Journal | Cell Signal | Volume | 18 |
| Issue | 10 | Pages | 1695-701 |
| PubMed ID | 16504475 | Mgi Jnum | J:129252 |
| Mgi Id | MGI:3768944 | Doi | 10.1016/j.cellsig.2006.01.009 |
| Citation | Kim J, et al. (2006) Vascular smooth muscle migration and proliferation in response to lysophosphatidic acid (LPA) is mediated by LPA receptors coupling to Gq. Cell Signal 18(10):1695-701 |
| abstractText | Many G protein-coupled receptors can couple to multiple G proteins to convey their intracellular signaling cascades. The receptors for lysophosphatidic acid (LPA) possess this ability. LPA receptors are important mediators of a wide variety of biological actions including cell migration, proliferation and survival which are processes that can all have a considerable impact on vascular smooth muscle (VSM) and blood vessels. To date, confirmation of G proteins involved has mostly relied on the inhibition of Gi-mediated signaling via pertussis toxin (PTx). We were interested in the specific involvement of LPA-Gq-mediated signaling therefore we isolated aorta VSM cells (VSMCs) from transgenic mice that express a peptide inhibitor of Gq, GqI, exclusively in VSM. We detected both LPA1 and LPA2 receptor expression in mouse VSM whereas LPA1 and LPA3 were expressed in rat VSM. SM22-GqI did not alter LPA-induced migration but it was sufficient to attenuate LPA-induced proliferation. GqI expression also attenuated LPA-induced ERK1/2 and Akt activation by 40-50%. To test the feasibility of this peptide as a potential therapeutic agent, we also generated adenovirus encoding the GqI. Transient expression of GqI was capable of inhibiting both LPA-induced migration and proliferation of VSMCs isolated from rat and mouse. Furthermore, ERK activation in response to LPA was also attenuated in VSMCs with Adv-GqI. Therefore, LPA receptors couple to Gq in VSMC and mediate migration and proliferation which may be mediated through activation of ERK1/2 and Akt. Our data also suggest that both chronic and transient expression of the GqI peptide is an effective strategy to lower Gq-mediated LPA signaling and may be a successful therapeutic strategy to combat diseases with enhanced VSM growth such as occurs following angioplasty or stent implantation. |
