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Melatonin alleviates hyperoxia-induced lung injury through elevating MSC exosomal miR-18a-5p expression to repress PUM2 signaling.
Zou, Dongmei; Liao, Jinwen; Xiao, Min; Liu, Liang; Xu, Mingguo.
Afiliação
  • Zou D; The Department of Pediatric, Shenzhen Children's Hospital, China Medical University, Shenzhen, Guangdong, China.
  • Liao J; The Department of Pediatric, Longgang District Maternity & Child Healthcare Hospital of Shenzhen City, (Longgang Maternity and Child Institute of Shantou University Medical College), Shenzhen, Guangdong, China.
  • Xiao M; The Department of Pediatric, Shenzhen Children's Hospital, China Medical University, Shenzhen, Guangdong, China.
  • Liu L; The Department of Pediatric, Shenzhen Children's Hospital, China Medical University, Shenzhen, Guangdong, China.
  • Xu M; The Department of Pediatric, Shenzhen Children's Hospital, China Medical University, Shenzhen, Guangdong, China.
FASEB J ; 38(16): e70012, 2024 Aug 31.
Article em En | MEDLINE | ID: mdl-39183539
ABSTRACT
Mesenchymal stem cells (MSC)-derived exosomes (Exo) are a possible option for hyperoxia-induced lung injury (HLI). We wanted to see if melatonin (MT)-pretreated MSC-derived exosomes (MT-Exo) were more effective against HLI, and we also tried to figure out the underlying mechanism. HLI models were established by hyperoxia exposure. HE staining was adopted to analyze lung pathological changes. MTT and flow cytometry were used to determine cell viability and apoptosis, respectively. The mitochondrial membrane potential (MMP) was analyzed using the JC-1 probe. LDH, ROS, SOD, and GSH-Px levels were examined by the corresponding kits. The interactions between miR-18a-5p, PUM2, and DUB3 were analyzed by molecular interaction experiments. MT-Exo could effectively inhibit hyperoxia-induced oxidative stress, inflammatory injury, and apoptosis in lung epithelial cells, while these effects of MT-Exo were weakened by miR-18a-5p knockdown in MSCs. miR-18a-5p reduced PUM2 expression in MLE-12 cells by directly targeting PUM2. In addition, PUM2 inactivated the Nrf2/HO-1 signaling pathway by promoting DUB3 mRNA decay post-transcriptionally. As expected, PUM2 overexpression or DUB3 knockdown abolished the protective effect of MT-Exo on hyperoxia-induced lung epithelial cell injury. MT-Exo carrying miR-18a-5p reduced hyperoxia-mediated lung injury in mice through activating Nrf2/HO-1 pathway. MT reduced PUM2 expression and subsequently activated the DUB3/Nrf2/HO-1 signal axis by increasing miR-18a-5p expression in MSC-derived exosomes to alleviate HLI.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Hiperóxia / MicroRNAs / Exossomos / Lesão Pulmonar / Células-Tronco Mesenquimais / Melatonina Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Hiperóxia / MicroRNAs / Exossomos / Lesão Pulmonar / Células-Tronco Mesenquimais / Melatonina Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article