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Exosome-delivered miR-153 from Trichinella spiralis promotes apoptosis of intestinal epithelial cells by downregulating Bcl2.
Wang, Ruibiao; Lin, Lihao; Han, Yang; Li, Zhixin; Zhen, Jingbo; Zhang, Yuheng; Sun, Feng; Lu, Yixin.
Affiliation
  • Wang R; Heilongjiang Provincial Key Laboratory of Zoonosis, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
  • Lin L; Heilongjiang Provincial Key Laboratory of Zoonosis, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
  • Han Y; Heilongjiang Provincial Key Laboratory of Zoonosis, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
  • Li Z; Heilongjiang Provincial Key Laboratory of Zoonosis, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
  • Zhen J; Heilongjiang Provincial Key Laboratory of Zoonosis, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
  • Zhang Y; Heilongjiang Provincial Key Laboratory of Zoonosis, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
  • Sun F; Heilongjiang Provincial Key Laboratory of Zoonosis, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
  • Lu Y; Heilongjiang Provincial Key Laboratory of Zoonosis, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China. luyixin@neau.edu.cn.
Vet Res ; 54(1): 52, 2023 Jun 28.
Article in En | MEDLINE | ID: mdl-37381058
ABSTRACT
Trichinellosis, a helminthic zoonosis, exhibits a cosmopolitan distribution and is a public health concern. In previous studies, it was reported that the exosomes secreted by Trichinella spiralis larvae (TsExos) largely affected cell biological activities. miRNAs, as exosome-delivered cargoes, affect the biological activities of the host by targeting genes. The present study aimed to elucidate the mechanisms by which miRNAs interact with intestinal epithelial cells. First, a miRNA library of TsExos was constructed; then, based on high-throughput miRNA sequencing results, miR-153 and its predicted target genes, namely, Agap2, Bcl2 and Pten, were selected for follow-up studies. The dual-luciferase reporter assays revealed that miR-153 directly targeted Bcl2 and Pten. Furthermore, real-time qPCR and Western blotting revealed that only Bcl2 was downregulated by TsExo-delivered miR-153 in porcine intestinal epithelial cells (IPEC-J2). Bcl2, an important antiapoptotic protein, plays an essential role in cell apoptosis as a common intersecting molecule of various signal transduction pathways. Therefore, we hypothesized that miR-153 derived from TsExos causes cell apoptosis by targeting Bcl2. The results suggested that miR-153 could induce apoptosis, reduce mitochondrial membrane potential, affect cell proliferation, and cause damage and substantial oxidative stress. Furthermore, miR-153 coincubated with IPEC-J2 cells stimulated the accumulation of the proapoptotic proteins Bax and Bad, which belong to the Bcl2 family of proteins, and the apoptosis-implementing proteins Caspase 9 and Caspase 3. Moreover, studies have suggested that miR-153 can promote apoptosis by regulating the MAPK and p53 signalling pathways involved in apoptosis. Thus, exosome-mediated miR-153 delivery secreted by T. spiralis could induce apoptosis and affect the MAPK and p53 signalling pathways by downregulating Bcl2 in IPEC-J2 cells. The study highlights the mechanisms underlying the invasion of T. spiralis larva.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Trichinella spiralis / Exosomes Type of study: Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Animals Language: En Journal: Vet Res Journal subject: MEDICINA VETERINARIA Year: 2023 Type: Article Affiliation country: China

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Trichinella spiralis / Exosomes Type of study: Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Animals Language: En Journal: Vet Res Journal subject: MEDICINA VETERINARIA Year: 2023 Type: Article Affiliation country: China