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METTL3 promotes hyperoxia-induced pyroptosis in neonatal bronchopulmonary dysplasia by inhibiting ATG8-mediated autophagy.
Xu, Lili; Shi, Zhan; Pan, Zhaojun; Wu, Rong.
Afiliação
  • Xu L; Huai'an Maternity and Child Healthcare Hospital, Yangzhou University Medical College, Neonatal Medical Center, Huai'an, China.
  • Shi Z; Huai'an Maternity and Child Healthcare Hospital, Yangzhou University Medical College, Neonatal Medical Center, Huai'an, China.
  • Pan Z; Huai'an Maternity and Child Healthcare Hospital, Yangzhou University Medical College, Neonatal Medical Center, Huai'an, China.
  • Wu R; Huai'an Maternity and Child Healthcare Hospital, Yangzhou University Medical College, Neonatal Medical Center, Huai'an, China. Electronic address: wr618@126.com.
Clinics (Sao Paulo) ; 78: 100253, 2023.
Article em En | MEDLINE | ID: mdl-37478627
OBJECTIVES: N6-Methyladenosine (m6A) modification plays a vital role in lung disorders. However, the potential of m6A in neonatal Bronchopulmonary Dysplasia (BPD) has not been reported. This study aimed to investigate the roles of METTL3 in BPD. METHODS: BPD models were established by hyperoxia in vivo and in vitro. Histological analysis was determined using HE staining. Gene expression was determined using Western blotting, qRT-PCR, and immunofluorescence. The release of IL-1ß and IL-18 was detected using ELISA. The m6A sites of ATG8 were predicted by SCRAPM and verified by MeRIP assay. The location of GSDMD and ATG8 was determined by FISH assay. The interaction between ATG8 and GSDMD was detected using Coimmunoprecipitation (Co-IP). Cell pyroptosis was determined using flow cytometry and TUNEL assays. RESULTS: METTL3 was overexpressed in BPD, which was accompanied by an increase in m6A levels. Interestingly, METTL3 suppressed hyperoxia-mediated damage and pyroptosis in BEAS-2B cells and promoted cell autophagy. METTL3-mediated m6A modification of ATG8 suppressed its expression and disrupted the interaction between ATG8 and GSDMD. However, autophagy inhibition induced pyroptosis in BEAS-2B cells. In vivo assays showed that METTL3-mediated autophagy inhibition induced a decrease in the radial alveolar count and an increase in the mean linear intercept and promoted cell pyroptosis. CONCLUSION: In conclusion, METTL3-mediated cell pyroptosis promotes BPD by regulating the m6A modification of ATG8. This may provide new insight into the development of BPD.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Displasia Broncopulmonar / Hiperóxia Tipo de estudo: Prognostic_studies Limite: Humans / Newborn Idioma: En Revista: Clinics (Sao Paulo) Assunto da revista: MEDICINA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
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XML
PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Displasia Broncopulmonar / Hiperóxia Tipo de estudo: Prognostic_studies Limite: Humans / Newborn Idioma: En Revista: Clinics (Sao Paulo) Assunto da revista: MEDICINA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China País de publicação: Estados Unidos