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Exosomes regulate SIRT3-related autophagy by delivering miR-421 to regulate macrophage polarization and participate in OSA-related NAFLD.
Yang, Li; Liu, Shijie; He, Yan; Gan, Lulu; Ni, Qing; Dai, Anni; Mu, Changhuan; Liu, Qian; Chen, Hongyan; Lu, Hongying; Sun, Ruixue.
Afiliação
  • Yang L; Hypertension Center, Yan 'an Hospital of Kunming Medical University, 245 Renmin East Road, Panlong District, Kunming City, 650000, Yunnan Province, China. yl13330466619@163.com.
  • Liu S; Kunming Technical Diagnosis and Treatment Center for Refractory Hypertension, Kunming Medical University, 245 Renmin East Road, Panlong District, Kunming City, 650000, Yunnan Province, China. yl13330466619@163.com.
  • He Y; Hypertension Center, Yan 'an Hospital of Kunming Medical University, 245 Renmin East Road, Panlong District, Kunming City, 650000, Yunnan Province, China.
  • Gan L; Kunming Technical Diagnosis and Treatment Center for Refractory Hypertension, Kunming Medical University, 245 Renmin East Road, Panlong District, Kunming City, 650000, Yunnan Province, China.
  • Ni Q; Hypertension Center, Yan 'an Hospital of Kunming Medical University, 245 Renmin East Road, Panlong District, Kunming City, 650000, Yunnan Province, China.
  • Dai A; Kunming Technical Diagnosis and Treatment Center for Refractory Hypertension, Kunming Medical University, 245 Renmin East Road, Panlong District, Kunming City, 650000, Yunnan Province, China.
  • Mu C; Hypertension Center, Yan 'an Hospital of Kunming Medical University, 245 Renmin East Road, Panlong District, Kunming City, 650000, Yunnan Province, China.
  • Liu Q; Kunming Technical Diagnosis and Treatment Center for Refractory Hypertension, Kunming Medical University, 245 Renmin East Road, Panlong District, Kunming City, 650000, Yunnan Province, China.
  • Chen H; Hypertension Center, Yan 'an Hospital of Kunming Medical University, 245 Renmin East Road, Panlong District, Kunming City, 650000, Yunnan Province, China.
  • Lu H; Kunming Technical Diagnosis and Treatment Center for Refractory Hypertension, Kunming Medical University, 245 Renmin East Road, Panlong District, Kunming City, 650000, Yunnan Province, China.
  • Sun R; Hypertension Center, Yan 'an Hospital of Kunming Medical University, 245 Renmin East Road, Panlong District, Kunming City, 650000, Yunnan Province, China.
J Transl Med ; 22(1): 475, 2024 May 19.
Article em En | MEDLINE | ID: mdl-38764033
ABSTRACT

PURPOSE:

To analyze the role of and mechanism underlying obstructive sleep apnea (OSA)-derived exosomes in inducing non-alcoholic fatty liver (NAFLD).

METHODS:

The role of OSA-derived exosomes was analyzed in inducing hepatocyte fat accumulation in mice models both in vivo and in vitro.

RESULTS:

OSA-derived exosomes caused fat accumulation and macrophage activation in the liver tissue. These exosomes promoted fat accumulation; steatosis was more noticeable in the presence of macrophages. Macrophages could internalize OSA-derived exosomes, which promoted macrophage polarization to the M1 type. Moreover, it inhibited sirtuin-3 (SIRT3)/AMP-activated protein kinase (AMPK) and autophagy and promoted the activation of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasomes. The use of 3-methyladenine (3-MA) to inhibit autophagy blocked NLRP3 inflammasome activation and inhibited the M1 polarization of macrophages. miR-421 targeting inhibited SIRT3 protein expression in the macrophages. miR-421 was significantly increased in OSA-derived exosomes. Additionally, miR-421 levels were increased in OSA + NAFLD mice- and patient-derived exosomes. In the liver tissues of OSA and OSA + NAFLD mice, miR-421 displayed similar co-localization with the macrophages. Intermittent hypoxia-induced hepatocytes deliver miR-421 to the macrophages via exosomes to inhibit SIRT3, thereby participating in macrophage M1 polarization. After OSA and NAFLD modeling in miR-421-/- mice, liver steatosis and M1 polarization were significantly reduced. Additionally, in the case of miR-421 knockout, the inhibitory effects of OSA-derived exosomes on SIRT3 and autophagy were significantly alleviated. Furthermore, their effects on liver steatosis and macrophage M1 polarization were significantly reduced.

CONCLUSIONS:

OSA promotes the delivery of miR-421 from the hepatocytes to macrophages. Additionally, it promotes M1 polarization by regulating the SIRT3/AMPK-autophagy pathway, thereby causing NAFLD.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autofagia / Polaridade Celular / Apneia Obstrutiva do Sono / MicroRNAs / Exossomos / Sirtuína 3 / Hepatopatia Gordurosa não Alcoólica / Macrófagos Limite: Animals / Humans / Male Idioma: En Revista: J Transl Med Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autofagia / Polaridade Celular / Apneia Obstrutiva do Sono / MicroRNAs / Exossomos / Sirtuína 3 / Hepatopatia Gordurosa não Alcoólica / Macrófagos Limite: Animals / Humans / Male Idioma: En Revista: J Transl Med Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China