Upregulation of endothelial cell-derived exosomal microRNA-125b-5p protects from sepsis-induced acute lung injury by inhibiting topoisomerase II alpha

Jiang, Lijing; Ni, Jindi; Shen, Guofeng; Xia, Zhuye; Zhang, Lu; Xia, Shihong; Pan, Shengfu; Qu, Hongping; Li, Xiang

doi:10.1007/s00011-020-01415-0

Cited by 26 publications

(25 citation statements)

References 31 publications

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“…Inhibition of apoptosis could contribute to therapeutic strategies for sepsis-induced acute lung injury. 35 Apoptosis is usually initiated by Bcl-2 and Bax followed by sequential activation of Caspase8 and Caspase3. 36 Activated Caspase3 is cleaved and further contacts the downstream effector PARP1, which finally induces apoptosis of neural cells.…”

Section: Discussionmentioning

confidence: 99%

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GYY4137 protected the integrity of the blood‐brain barrier via activation of the Nrf2/ARE pathway in mice with sepsis

Cui

Chen

et al. 2021

The FASEB Journal

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Injury to the blood‐brain barrier (BBB) plays a vital role in sepsis‐associated encephalopathy (SAE), which is one of the most common complications of sepsis. GYY4137, a new synthetic compound of hydrogen sulfide (H2S), has extensive biological benefits. In this study, we focused on the protective effects of GYY4137 on the BBB in septic mice and the underlying mechanisms. The results suggested that whether administrated at the same time or 3 hours after LPS injection, GYY4137 both significantly alleviated the clinical symptoms and the long‐term prognosis. Besides, GYY4137 improved the pathological abnormalities of septic mice. Moreover, the degradation of tight junctions in the BBB was considerably inhibited by GYY4137. In addition, GYY4137 significantly attenuated inflammation and apoptosis in the brain. Furthermore, GYY4137 activated the Nrf2/ARE pathway through the sulfhydrylation of Keap1 and inhibited oxidative stress. ML385, the specific inhibitor of Nrf2, significantly reversed the protective effects of GYY4137 in sepsis mice. In conclusion, this study indicated that through the sulfhydrylation of Keap1, GYY4137 activated the Nrf2/ARE pathway and exerted anti‐inflammatory, anti‐apoptotic and antioxidant effects in septic mice that consequently protected the integrity of the BBB and improved the clinical outcome of sepsis. Our findings suggest that GYY4137 might be a promising agent for the treatment of SAE.

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Section: Discussionmentioning

confidence: 99%

“…According to previous studies, most of the causes of SAE eventually lead to neural apoptosis. Inhibition of apoptosis could contribute to therapeutic strategies for sepsis‐induced acute lung injury 35 . Apoptosis is usually initiated by Bcl‐2 and Bax followed by sequential activation of Caspase8 and Caspase3 36 .…”

Section: Discussionmentioning

confidence: 99%

GYY4137 protected the integrity of the blood‐brain barrier via activation of the Nrf2/ARE pathway in mice with sepsis

Cui

Chen

et al. 2021

The FASEB Journal

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“…Jiang et al. found that endothelial cell-derived exosomes could inhibit topoisomerase II α (TOP2A) expression, resulting in a protective role in sepsis-induced ALI ( 143 ). This effect was achieved by the transfer of miR-125b-5p.…”

Section: The Safety and Efficacy Of Exosomes In Animal Experiments An...mentioning

confidence: 99%

Advances in the use of exosomes for the treatment of ALI/ARDS

2022

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Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a critical clinical syndrome with high morbidity and mortality. Currently, the primary treatment for ALI/ARDS is mainly symptomatic therapy such as mechanical ventilation and fluid management. Due to the lack of effective treatment strategies, most ALI/ARDS patients face a poor prognosis. The discovery of exosomes has created a promising prospect for the treatment of ALI/ARDS. Exosomes can exert anti-inflammatory effects, inhibit apoptosis, and promote cell regeneration. The microRNA contained in exosomes can participate in intercellular communication and play an immunomodulatory role in ALI/ARDS disease models. This review discusses the possible mechanisms of exosomes in ALI/ARDS to facilitate the development of innovative treatments for ALI/ARDS.

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“…In an acute lung injury (ALI) mouse model established by cecal ligation puncture (CLP), miR-125 in exosomes derived from endothelial cells promoted VEGF expression, inflammatory response, improved pathological changes, restrained lung water content, protein content in bronchoalveolar lavage fluid, and cell apoptosis by targeting TOP2A [ 30 ]. In an LPS-induced ALI rat model, miR-384 in exosomes derived from BMSC alleviated pathological changes in lung, pulmonary vascular permeability, and attenuated the inflammatory response by targeting Beclin-1 [ 31 ].…”

Section: Main Textmentioning

confidence: 99%

The Extracellular MicroRNAs on Inflammation: A Literature Review of Rodent Studies

Lee

Kim

2022

Biomedicines

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Inflammation is an indispensable biological process stimulated by infection and injuries. Inflammatory mechanisms related to extracellular vesicles (EVs), which are small membrane structures carrying various molecules, were summarized in this review. Emerging evidence from animal studies has highlighted the role of EVs in modulating inflammatory responses, by transporting various molecules involved in host defense. In this review, we have discussed the role of EV miRNAs in inflammation. Rodent studies associated with extracellular miRNAs in inflammatory diseases, published from 2012 to 2022, were explored from PUBMED, EMBASE, and MEDLINE. A total of 95 studies were reviewed. In summary, EV-associated miRNAs play a key role in various diseases, including organ injury, immune dysfunction, neurological disease, metabolic syndrome, vesicular disease, arthritis, cancer, and other inflammatory diseases. Diverse EV-associated miRNAs regulate inflammasome activation and pro- and anti-inflammatory cytokine levels by targeting genes.

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Upregulation of endothelial cell-derived exosomal microRNA-125b-5p protects from sepsis-induced acute lung injury by inhibiting topoisomerase II alpha

Cited by 26 publications

References 31 publications

GYY4137 protected the integrity of the blood‐brain barrier via activation of the Nrf2/ARE pathway in mice with sepsis

GYY4137 protected the integrity of the blood‐brain barrier via activation of the Nrf2/ARE pathway in mice with sepsis

Advances in the use of exosomes for the treatment of ALI/ARDS

The Extracellular MicroRNAs on Inflammation: A Literature Review of Rodent Studies

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