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Exosomes Derived from Human Circulating Endothelial Progenitor Cells Ameliorates Acute Lung Injury by Transferring miR-126
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A3884 - Exosomes Derived from Human Circulating Endothelial Progenitor Cells Ameliorates Acute Lung Injury by Transferring miR-126
Author Block: W. Xu; Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
RATIONALE: Endothelial progenitor cell (EPC) has immense potential to attenuate pulmonary inflammation and injury. As a pivotal paracrine entity of stem cells, whether circulating EPC-derived exosomes (CEPC-Exos) contribute to acute lung injury (ALI) and its mechanism remains unknown. METHODS: Exosomes were purified from conditional medium of CEPCs that obtained from human peripheral blood mononuclear cells, and then characterized by electron micrograph and western blot. A rat model of lipopolysaccharide (LPS) induced ALI was established in vivo and transplanted with CEPC-Exos. After co-cultured with CEPCs, we measured the levels of key microRNAs in HUVECs treated with 10 μM GW4869. CEPCs were transfected with anti-miR-NC and anti-miR-126 respectively. The underlining mechanisms of CEPC-Exos were explored in vitro endothelial functional assays including the TEER, proliferation (CKK-8), angiogenesis, migration and apoptosis. RESULTS: Administration of CEPC-Exos ameliorated LPS-induced ALI and restored the integrity of pulmonary in vivo. CEPC-Exos enhanced the proliferation, migration, tube formation and inhibited apoptosis of the HUVECs. Furthermore, we found that miR-126 was enriched in CEPC-Exos and can be delivered onto endothelial cells. Modification of CEPCs through miR-126-3p knockdown can diminish their exosomes function, indicative of the abilities of CEPC-Exos to protect against LPS were inherited by the horizontal shuttled miR-126. Luciferase reporter assays confirmed that miR-126 targeted SPRED1. Transferred miR-126 to target endothelial cells with subsequent downregulation of SPRED1 and PIK3R2 could partly promote the PI3K/AKT/eNOS and RAF1/ERK signaling pathways, so that to be implicated in the reparative process. CONCLUSIONS: Our study revealed a novel role of exosomal miR-126 in EPC-mediated therapy. Application of CEPC-Exos might represent an attractive strategy in ALI/ARDS.
Author Block: W. Xu; Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
RATIONALE: Endothelial progenitor cell (EPC) has immense potential to attenuate pulmonary inflammation and injury. As a pivotal paracrine entity of stem cells, whether circulating EPC-derived exosomes (CEPC-Exos) contribute to acute lung injury (ALI) and its mechanism remains unknown. METHODS: Exosomes were purified from conditional medium of CEPCs that obtained from human peripheral blood mononuclear cells, and then characterized by electron micrograph and western blot. A rat model of lipopolysaccharide (LPS) induced ALI was established in vivo and transplanted with CEPC-Exos. After co-cultured with CEPCs, we measured the levels of key microRNAs in HUVECs treated with 10 μM GW4869. CEPCs were transfected with anti-miR-NC and anti-miR-126 respectively. The underlining mechanisms of CEPC-Exos were explored in vitro endothelial functional assays including the TEER, proliferation (CKK-8), angiogenesis, migration and apoptosis. RESULTS: Administration of CEPC-Exos ameliorated LPS-induced ALI and restored the integrity of pulmonary in vivo. CEPC-Exos enhanced the proliferation, migration, tube formation and inhibited apoptosis of the HUVECs. Furthermore, we found that miR-126 was enriched in CEPC-Exos and can be delivered onto endothelial cells. Modification of CEPCs through miR-126-3p knockdown can diminish their exosomes function, indicative of the abilities of CEPC-Exos to protect against LPS were inherited by the horizontal shuttled miR-126. Luciferase reporter assays confirmed that miR-126 targeted SPRED1. Transferred miR-126 to target endothelial cells with subsequent downregulation of SPRED1 and PIK3R2 could partly promote the PI3K/AKT/eNOS and RAF1/ERK signaling pathways, so that to be implicated in the reparative process. CONCLUSIONS: Our study revealed a novel role of exosomal miR-126 in EPC-mediated therapy. Application of CEPC-Exos might represent an attractive strategy in ALI/ARDS.
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