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Serum Exosome-Derived microRNA-193a-5p and miR-381-3p Regulate Adenosine 5'-Monophosphate-Activated Protein Kinase/Transforming Growth Factor Beta/Smad2/3 Signaling Pathway and Promote Fibrogenesis.
Wang, Sihao; Chen, Yan; Lei, Guanglin; Ma, Xuemei; An, Linjing; Wang, Han; Song, Zheng; Lin, Li; He, Quanwei; Xu, Ran; Zhan, Xiaoyan; Bai, Zhaofang; Yang, Yongping.
Afiliação
  • Wang S; Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
  • Chen Y; Medical School of Chinese PLA, Beijing, China.
  • Lei G; Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
  • Ma X; Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
  • An L; Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
  • Wang H; Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
  • Song Z; Department of Blood Transfusion, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
  • Lin L; Peking University 302 Clinical Medical School, Beijing, China.
  • He Q; Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
  • Xu R; Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
  • Zhan X; Medical School of Chinese PLA, Beijing, China.
  • Bai Z; Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
  • Yang Y; Medical School of Chinese PLA, Beijing, China.
Clin Transl Gastroenterol ; 15(2): e00662, 2024 02 01.
Article em En | MEDLINE | ID: mdl-38099588
ABSTRACT

INTRODUCTION:

Liver fibrosis results from chronic liver injury and inflammation, often leading to cirrhosis, liver failure, portal hypertension, and hepatocellular carcinoma. Progress has been made in understanding the molecular mechanisms underlying hepatic fibrosis; however, translating this knowledge into effective therapies for disease regression remains a challenge, with considerably few interventions having entered clinical validation. The roles of exosomes during fibrogenesis and their potential as a therapeutic approach for reversing fibrosis have gained significant interest. This study aimed to investigate the association between microRNAs (miRNAs) derived from serum exosomes and liver fibrosis and to evaluate the effect of serum exosomes on fibrogenesis and fibrosis reversal, while identifying the underlying mechanism.

METHODS:

Using serum samples collected from healthy adults and paired histologic patients with advanced fibrosis or cirrhosis, we extracted human serum exosomes by ultrahigh-speed centrifugation. Transcriptomic analysis was conducted to identify dysregulated exosome-derived miRNAs. Liver fibrosis-related molecules were determined by qRT-PCR, Western blot, Masson staining, and immunohistochemical staining. In addition, we analyzed the importance of serum exosome-derived miRNA expression levels in 42 patients with advanced fibrosis or cirrhosis.

RESULTS:

Exosome-derived miR-193a-5p and miR-381-3p were associated with fibrogenesis, as determined by transcriptomic screening. Compared with healthy control group, the high expression of serum exosome-derived miR-193a-5p and miR-381-3 in chronic hepatitis B (n = 42) was closely associated with advanced liver fibrosis and cirrhosis. In vitro , exosome-derived miRNA-193a-5p and miR-381-3p upregulated the expression of α-smooth muscle actin, collagen 1a1, and tissue inhibitors of metalloproteinase 1 in the human hepatic stellate cell line at both mRNA and protein levels.

DISCUSSION:

Serum exosome-derived miR-193a-5p and miR-381-3p regulated the adenosine 5'-monophosphate-activated protein kinase/transforming growth factor beta/Smad2/3 signaling pathway and promoted fibrogenesis.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: MicroRNAs / Exossomos Limite: Adult / Humans Idioma: En Revista: Clin Transl Gastroenterol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: MicroRNAs / Exossomos Limite: Adult / Humans Idioma: En Revista: Clin Transl Gastroenterol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China