Thrombospondin‐1 (TSP1) is involved in corneal wound healing caused by chemical injury. Herein, we examined the effects of TSP1 on hypoxia‐induced damages and wound‐healing activity in human corneal epithelial (HCE) cells. Exosomal protein expression was determined using liquid chromatography‐tandem mass spectrometry, and HCE cell migration and motility were examined through wound‐healing assay and time‐lapse microscopy. Reestablishment of cell junctions by TSP1 was assessed through confocal microscopy and 3D image reconstruction. Our results show that CoCl2‐induced hypoxia promoted HCE cell death by paraptosis. TSP1 protected these cells against paraptosis by attenuating mitochondrial membrane potential depletion, swelling and dilation of endoplasmic reticulum and mitochondria, and mitochondrial fission. Exosomes isolated from HCE cells treated with TSP1 contained wound healing‐associated proteins that were taken up by HCE cells to promote tissue remodeling and repair. TSP1 protected HCE cells against hypoxia‐induced damages and inhibited paraptosis progression by promoting cell migration, cell‐cell adhesion, and extracellular matrix remodeling. These findings indicate that TSP1 ameliorates hypoxia‐induced paraptosis in HCE cells and promotes wound healing and remodeling by regulating exosomal protein expression. TSP1 may, therefore, play important roles in the treatment of hypoxia‐associated corneal diseases.

中文翻译：

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血小板反应蛋白 1 诱导的外泌体蛋白减弱缺氧诱导的角膜上皮细胞凋亡并促进伤口愈合

血小板反应蛋白-1 (TSP1) 参与化学损伤引起的角膜伤口愈合。在此，我们研究了 TSP1 对人角膜上皮 (HCE) 细胞缺氧诱导的损伤和伤口愈合活性的影响。使用液相色谱-串联质谱法测定外泌体蛋白表达，并通过伤口愈合试验和延时显微镜检查 HCE 细胞迁移和运动。通过共聚焦显微镜和 3D 图像重建评估了 TSP1 对细胞连接的重建。我们的结果表明，CoCl2 诱导的缺氧促进了 HCE 细胞的凋亡。TSP1 通过减弱线粒体膜电位耗竭、内质网和线粒体的肿胀和扩张以及线粒体裂变来保护这些细胞免于凋亡。从用 TSP1 处理的 HCE 细胞中分离的外泌体含有伤口愈合相关蛋白，这些蛋白被 HCE 细胞吸收以促进组织重塑和修复。TSP1 通过促进细胞迁移、细胞间粘附和细胞外基质重塑来保护 HCE 细胞免受缺氧诱导的损伤并抑制细胞凋亡的进展。这些发现表明 TSP1 改善了 HCE 细胞中缺氧诱导的细胞凋亡，并通过调节外泌体蛋白表达促进伤口愈合和重塑。因此，TSP1 可能在缺氧相关角膜疾病的治疗中发挥重要作用。TSP1 通过促进细胞迁移、细胞间粘附和细胞外基质重塑来保护 HCE 细胞免受缺氧诱导的损伤并抑制细胞凋亡的进展。这些发现表明 TSP1 改善了 HCE 细胞中缺氧诱导的细胞凋亡，并通过调节外泌体蛋白表达促进伤口愈合和重塑。因此，TSP1 可能在缺氧相关角膜疾病的治疗中发挥重要作用。TSP1 通过促进细胞迁移、细胞间粘附和细胞外基质重塑来保护 HCE 细胞免受缺氧诱导的损伤并抑制细胞凋亡的进展。这些发现表明 TSP1 改善了 HCE 细胞中缺氧诱导的细胞凋亡，并通过调节外泌体蛋白表达促进伤口愈合和重塑。因此，TSP1 可能在缺氧相关角膜疾病的治疗中发挥重要作用。