Published online Nov 28, 2013. doi: 10.5320/wjr.v3.i3.77
Revised: October 3, 2013
Accepted: November 18, 2013
Published online: November 28, 2013
Processing time: 96 Days and 4.5 Hours
Autotaxin (ATX or ENPP2) is a secreted glycoprotein widely present in biological fluids. ATX primarily functions as a plasma lysophospholipase D and is largely responsible for the bulk of lysophosphatidic acid (LPA) production in the plasma and at inflamed and/or malignant sites. LPA is a phospholipid mediator produced in various conditions both in cells and in biological fluids, and it evokes growth-factor-like responses, including cell growth, survival, differentiation and motility, in almost all cell types. The large variety of LPA effector functions is attributed to at least six G-protein coupled LPA receptors (LPARs) with overlapping specificities and widespread distribution. Increased ATX/LPA/LPAR levels have been detected in a large variety of cancers and transformed cell lines, as well as in non-malignant inflamed tissues, suggesting a possible involvement of ATX in chronic inflammatory disorders and cancer. In this review, we focus exclusively on the role of the ATX/LPA axis in pulmonary pathophysiology, analysing the effects of ATX/LPA on pulmonary cells and leukocytes in vitro and in the context of pulmonary pathophysiological situations in vivo and in human diseases.
Core tip: In the lungs, autotaxin (ATX) is constitutively expressed in the bronchial epithelium, and all pulmonary cell types express some amount of lysophosphatidic acid (LPA) receptor. LPA affects all pulmonary cell types, mainly promoting a pro-inflammatory state. Increased ATX/LPA levels have been detected in various pathophysiological situations, both in mice and humans, including acute, allergic or chronic pulmonary inflammation; fibrosis; and lung cancer. Genetic or pharmacologic interventions targeting the ATX/LPA axis have proved beneficial for modelled disease management in animal models, establishing the ATX/LPA axis as a possible therapeutic target.