The State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, Hohhot, Inner Mongolia, China.
College of Life Sciences, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China; and.
Am J Respir Cell Mol Biol. 2023 Feb;68(2):161-175. doi: 10.1165/rcmb.2021-0331OC.
Acute respiratory distress syndrome/acute lung injury (ARDS/ALI) involves acute respiratory failure characterized by vascular endothelial and lung alveolar epithelial injury. 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 G and G, respectively. Activation of extracellular signal-related kinase 1/2, or ERK1/2, was related to LPA-induced EPC proliferation but not migration. LPA/Lpar1-mediated G protein was also shown to be involved in promoting VEGF expression and inhibiting IL-1α 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 infected 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.
急性呼吸窘迫综合征/急性肺损伤（ARDS/ALI）涉及以血管内皮和肺泡上皮损伤为特征的急性呼吸衰竭。内皮祖细胞（EPCs）可介导血管生成。然而，EPCs 的局限性，如低存活率和分化能力，被认为抑制了自体细胞疗法的效果。本研究表明，溶血磷脂酸（LPA），一种无免疫原性的生物活性小分子，参与了人脐带间充质干细胞的存活和抗凋亡作用。本研究旨在探讨 LPA 是否能提高 EPC 的存活率，增强 EPC 在 ARDS 中的细胞治疗效果，这些结果将扩大 LPA 在干细胞和再生医学中的应用。LPA 促进了 EPC 的集落形成、增殖和迁移，并上调了 EPC 中血管内皮衍生生长因子（VEGF）的表达。LPA 预处理移植的 EPCs 通过增加大鼠肺部 EPCs 的数量来提高治疗效果。LPA 通过分别与 G 和 G 偶联，增强了 EPC 的增殖和迁移。细胞外信号调节激酶 1/2（ERK1/2）的激活与 LPA 诱导的 EPC 增殖有关，但与迁移无关。LPA/Lpar1 介导的 G 蛋白也被证明参与了促进 EPC 中 VEGF 的表达和抑制 IL-1α 的表达。肺损伤后会出现低浓度的 LPA；因此，LPA 的恢复可能会促进 ARDS 中血管内皮细胞的稳态和肺修复。LPA 的吸入显著促进了内源性 EPCs 向肺部的归巢，并减轻了 LPS 诱导的 ALI 大鼠和感染小鼠的肺损伤。综上所述，这些数据表明，LPA/Lpar1 介导的 EPC 作用参与了在生理条件下维持血管内皮细胞的稳态和肺组织的修复。
