miR-125b-5p in adipose derived stem cells exosome alleviates pulmonary microvascular endothelial cells ferroptosis via Keap1/Nrf2/GPX4 in sepsis lung injury

Shen, Kuo; Wang, Xujie; Wang, Yunwei; Jia, Yong; Zhang, Yue; Wang, Kejia; Luo, Liang; Cai, Wenju; Li, Jin; Li, Shaohui; Du, Yuting; Zhang, Lixia; Zhang, Hao; Chen, Yuxi; Xu, Chaolei; Zhang, Jinxin; Wang, Ruizhi; Yang, Xuekang; Wang, Yunchuan; Hu, Dahai

doi:10.1016/j.redox.2023.102655

Cited by 100 publications

(47 citation statements)

References 54 publications

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“…Recently, many studies have revealed that ferroptosis occurs in endothelial cells. It is reported that ferroptosis occurred in pulmonary microvascular endothelial cells and that Keap1/Nrf2/GPX4 signaling regulated this process [33]. ZnONPs induced lipid peroxidation in ECs, and the ferrostatin-1 (lipid-ROS scavenger) and the DFO (iron chelator) could alleviate ZnONP-stimulated ferroptosis in ECs [34].…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cell-derived Exosomal miR-125b-5p Suppressed Retinal Microvascular Endothelial Cell Ferroptosis by Targeting P53 in Diabetic Retinopathy

Tong,

Chen,

Xiang

et al. 2024

Preprint

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Progressive endothelial cell injury of retinal vascular is a vital factor in diabetic retinopathy (DR) pathogenesis. Mesenchymal stromal cells-derived small extracellular vesicles (MSC-sEVs) showed beneficial effects on DR. However, the effects of MSC-sEVs in endothelial dysfunction of DR and the mechanism is still unclear. In this study, MSC-sEVs mitigated retinal blood-retina barrier(BRB) impairment in rats with streptozotocin (STZ)-induced DR by reducing ferroptosis in vivo and in vitro. MSC-sEVs miRNA sequencing analysis revealed that miR-125b-5p may mediate HRMEC ferroptosis and P53 as a downstream target based on dual-luciferase reporter assays. Silencing miR-125b-5p in MSC-sEVs reversed the therapeutic effects of MSC-sEVs on rats with DR and advanced glycation end products (AGE)-treated HRMECs. Additionally, overexpression of miR-125b-5p could diminish ferroptosis in HRMECs, and this effect could be effectively reversed by overexpressing P53. This study indicated the potential therapeutic effect of MSC-sEVs on vascular endothelial function maintenance and that the delivery of sEVs carrying miR-125b-5p could prevent endothelial cell ferroptosis by inhibiting P53, thereby protecting the BRB.

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Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cell-derived Exosomal miR-125b-5p Suppressed Retinal Microvascular Endothelial Cell Ferroptosis by Targeting P53 in Diabetic Retinopathy

Tong,

Chen,

Xiang

et al. 2024

Preprint

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“…Furthermore, Shen et al reported that miR-125b-5p in MSC-EVs can attenuate ferroptosis in HPMVECs due to excessive inflammation in ALI by regulating the expression of Keap1/NRF2/GPX4. [33] Therefore, miRNA-125b was chosen to be loaded into the EVs. EC-EVs serving as nano vectors loaded with miRNA-125b not only promoted miRNA delivery in vivo but also exhibited improved therapeutic efficiency, achieving a "two birds with one stone" effect.…”

Section: Discussionmentioning

confidence: 99%

Endothelium‐Derived Engineered Extracellular Vesicles Protect the Pulmonary Endothelial Barrier in Acute Lung Injury

Gu,

Sun,

Liu

et al. 2023

Advanced Science

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Acute lung injury (ALI) is a severe respiratory disease with a high mortality rate. The integrity of the pulmonary endothelial barrier influences the development and prognosis of ALI. Therefore, it has become an important target for ALI treatment. Extracellular vesicles (EVs) are promising nanotherapeutic agents against ALI. Herein, endothelium‐derived engineered extracellular vesicles (eEVs) that deliver microRNA‐125b‐5p (miRNA‐125b) to lung tissues exerting a protective effect on endothelial barrier integrity are reported. eEVs that are modified with lung microvascular endothelial cell‐targeting peptides (LET) exhibit a prolonged retention time in lung tissues and targeted lung microvascular endothelial cells in vivo and in vitro. To improve the efficacy of the EVs, miRNA‐125b is loaded into EVs. Finally, LET‐EVs‐miRNA‐125b is constructed. The results show that compared to the EVs, miRNA‐125b, and EVs‐miRNA‐125b, LET‐EVs‐miRNA‐125b exhibit the most significant treatment efficacy in ALI. Moreover, LET‐EVs‐miRNA‐125b is found to have an important protective effect on endothelial barrier integrity by inhibiting cell apoptosis, promoting angiogenesis, and protecting intercellular junctions. Sequencing analysis reveals that LET‐EVs‐miRNA‐125b downregulates early growth response‐1 (EGR1) levels, which may be a potential mechanism of action. Taken together, these findings suggest that LET‐EVs‐miRNA‐125b can treat ALI by protecting the endothelial barrier integrity.

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“…98 Shen et al isolated adipose-derive stem cell EVs (ADSCs-EVs) and discovered that specific delivery of miR-125b-5p by ADSCs-EVs in a sepsis model could inhibit the Keap1/Nrf2/GPX4 pathway, enhancing the effect of ferroptosis. 99 In addition, Jiang et al used exosomes from Osteosarcoma (OS) as carriers of miRNA-144-3p to promote ferroptosis and inhibit the proliferation, migration and invasion of osteosarcoma by regulating ZEB1. 100 Wu et al .…”

Section: Application Of Ferroptosis-based Nanomedicine Delivery Syste...mentioning

confidence: 99%

Recent progress in biomaterials-driven ferroptosis for cancer therapy

Xiao,

Xiong,

Zhou

et al. 2024

Biomater. Sci.

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miR-125b-5p in adipose derived stem cells exosome alleviates pulmonary microvascular endothelial cells ferroptosis via Keap1/Nrf2/GPX4 in sepsis lung injury

Cited by 100 publications

References 54 publications

Mesenchymal Stem Cell-derived Exosomal miR-125b-5p Suppressed Retinal Microvascular Endothelial Cell Ferroptosis by Targeting P53 in Diabetic Retinopathy

Mesenchymal Stem Cell-derived Exosomal miR-125b-5p Suppressed Retinal Microvascular Endothelial Cell Ferroptosis by Targeting P53 in Diabetic Retinopathy

Endothelium‐Derived Engineered Extracellular Vesicles Protect the Pulmonary Endothelial Barrier in Acute Lung Injury

Recent progress in biomaterials-driven ferroptosis for cancer therapy

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