| First Author | Lee SJ | Year | 2013 |
| Journal | Mol Cell Biol | Volume | 33 |
| Issue | 10 | Pages | 2016-28 |
| PubMed ID | 23478264 | Mgi Jnum | J:204035 |
| Mgi Id | MGI:5529431 | Doi | 10.1128/MCB.00038-13 |
| Citation | Lee SJ, et al. (2013) Distinct phospholipase C-beta isozymes mediate lysophosphatidic acid receptor 1 effects on intestinal epithelial homeostasis and wound closure. Mol Cell Biol 33(10):2016-28 |
| abstractText | Maintenance of the epithelial barrier in the intestinal tract is necessary to protect the host from the hostile luminal environment. Phospholipase C-beta (PLC-beta) has been implicated to control myriad signaling cascades. However, the biological effects of selective PLC-beta isozymes are poorly understood. We describe novel findings that lysophosphatidic acid (LPA) regulates PLC-beta1 and PLC-beta2 via two distinct pathways to enhance intestinal epithelial cell (IEC) proliferation and migration that facilitate wound closure and recovery of the intestinal epithelial barrier. LPA acting on the LPA1 receptor promotes IEC migration by facilitating the interaction of Galphaq with PLC-beta2. LPA-induced cell proliferation is PLC-beta1 dependent and involves translocation of Galphaq to the nucleus, where it interacts with PLC-beta1 to induce cell cycle progression. An in vivo study using LPA1-deficient mice (Lpar1(-/-)) shows a decreased number of proliferating IECs and migration along the crypt-luminal axis. Additionally, LPA enhances migration and proliferation of IECs in an LPA1-dependent manner, and Lpar1(-/-) mice display defective mucosal wound repair that requires cell proliferation and migration. These findings delineate novel LPA1-dependent lipid signaling that facilitates mucosal wound repair via spatial targeting of distinct PLC-betas within the cell. |
