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Endothelial progenitor cells (EPCs) can mediate vasculogenesis. However, the limitations of EPCs, such as low survival and differentiation, are believed to inhibit the effectiveness of autologous cell therapies. This study demonstrated that lysophosphatidic acid (LPA), a bioactive small molecule without immunogenicity, is involved in the survival and antiapoptotic effects in human umbilical cord mesenchymal stem cells. This study aimed to explore whether LPA improves the survival of EPCs, enhancing the cellular therapeutic efficacy in ARDS, and these results will expand the application of LPA in stem cells and regenerative medicine. LPA promoted the colony formation, proliferation, and migration of EPCs and upregulated the expression of vascular endothelial-derived growth factor (VEGF) in EPCs. LPA pretreatment of transplanted EPCs improved the therapeutic effect by increasing EPC numbers in the rat lungs. LPA enhanced EPC proliferation and migration through Lpar1 coupled to Gi\/o and Gq\/11, respectively. Activation of extracellular signal\u2013related kinase 1\/2, or ERK1\/2, was related to LPA-induced EPC proliferation but not migration. LPA\/Lpar1-mediated Gi\/o protein was also shown to be involved in promoting VEGF expression and inhibiting IL-1\u03b1 expression in EPCs. Low LPA concentrations are present after lung injury; thus, the restoration of LPA may promote endothelial cell homeostasis and lung repair in ARDS. Inhalation of LPA significantly promoted the homing of endogenous EPCs to the lung and reduced lung injury in both rats with LPS-induced ALI and Streptococcus pneumoniae\u2013infected mice. Taken together, these data indicated that LPA\/Lpar1-mediated effects in EPCs are involved in maintaining endothelial cell homeostasis and lung tissue repair under physiological conditions.<\/jats:p>","DOI":"10.1165\/rcmb.2021-0331oc","type":"journal-article","created":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T11:57:42Z","timestamp":1666785462000},"page":"161-175","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":4,"title":["Lpar1-mediated Effects in Endothelial Progenitor Cells Are Crucial for Lung Repair in Acute Respiratory Distress Syndrome\/Acute Lung Injury"],"prefix":"10.1093","volume":"68","author":[{"given":"Narengerile","family":"Li","sequence":"first","affiliation":[{"name":"The State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, Hohhot, Inner Mongolia, China"},{"name":"College of Life Sciences, Inner Mongolia Agricultural 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