Distinct Phospholipase C-β Isozymes Mediate Lysophosphatidic Acid Receptor 1 Effects on Intestinal Epithelial Homeostasis and Wound Closure

被引：45
作者：
Lee, Sei-Jung [1 ]
Leoni, Giovanna [2 ]
Neumann, Philipp-Alexander [2 ]
Chun, Jerold [3 ]
Nusrat, Asma [2 ]
Yun, C. Chris [1 ,4 ]
机构：
[1] Emory Univ, Sch Med, Dept Med, Div Digest Dis, Atlanta, GA 30322 USA
[2] Emory Univ, Sch Med, Dept Pathol & Lab Med, Emory Epithelial Pathobiol & Mucosal Inflammat Re, Atlanta, GA 30322 USA
[3] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA
[4] Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA USA
来源：
MOLECULAR AND CELLULAR BIOLOGY | 2013年 / 33卷 / 10期
关键词：
NA+/H+ EXCHANGER NHE3; COLON-CANCER; RHO-GTPASES; STEM-CELLS; IN-VIVO; NUCLEAR; LPA(1); ACTIVATION; ABSENCE; KINASE;
D O I：
10.1128/MCB.00038-13
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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-beta 1 and PLC-beta 2 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 LPA(1) receptor promotes IEC migration by facilitating the interaction of G alpha q with PLC-beta 2. LPA-induced cell proliferation is PLC-beta 1 dependent and involves translocation of G alpha q to the nucleus, where it interacts with PLC-beta 1 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 LPA(1)-dependent manner, and Lpar1(-/-) mice display defective mucosal wound repair that requires cell proliferation and migration. These findings delineate novel LPA(1)-dependent lipid signaling that facilitates mucosal wound repair via spatial targeting of distinct PLC-beta s within the cell.
引用
收藏
页码：2016 / 2028
页数：13
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