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Modulation of Ras signaling pathway by exosome miRNAs in T-2 toxin-induced chondrocyte injury.
Wang, Chaowei; Hu, Minhan; Yuan, Yuequan; Lv, Xi; Li, Shujin; Chen, Sijie; Zhang, Feiyu; Wu, Yifan; Zhang, Yu; Liu, Yanli; Chen, Feihong; Guo, Xiong; Ning, Yujie; Wang, Xi.
Afiliación
  • Wang C; School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, Shaanxi 710061, PR China.
  • Hu M; Xi'an Center for Disease Control and Prevention, Xi'an 710068, PR China.
  • Yuan Y; School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, Shaanxi 710061, PR China.
  • Lv X; School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, Shaanxi 710061, PR China.
  • Li S; School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, Shaanxi 710061, PR China.
  • Chen S; School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, Shaanxi 710061, PR China.
  • Zhang F; School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, Shaanxi 710061, PR China.
  • Wu Y; Department of Occupational and Environmental Health, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, PR China.
  • Zhang Y; Department of Occupational and Environmental Health, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, PR China.
  • Liu Y; Department of Occupational and Environmental Health, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, PR China.
  • Chen F; Department of Occupational and Environmental Health, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, PR China.
  • Guo X; School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, Shaanxi 710061, PR China; Clinical Research Center for Endemic Disease of Shaanxi Province, the Second Affiliated Ho
  • Ning Y; School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, Shaanxi 710061, PR China. Electronic address: ning461871077@xjtu.edu.cn.
  • Wang X; School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, Shaanxi 710061, PR China; Department of Occupational and Environmental Health, School of Public Health, Xi'an Jiaoto
Toxicology ; 506: 153858, 2024 Aug.
Article en En | MEDLINE | ID: mdl-38825033
ABSTRACT
This study aims to investigate the impact of T-2 toxin on the regulation of downstream target genes and signaling pathways through exosome-released miRNA in the development of cartilage damage in Kashin-Beck disease (KBD). Serum samples from KBD patients and supernatant from C28/I2 cells treated with T-2 toxin were collected for the purpose of comparing the differential expression of exosomal miRNA using absolute quantitative miRNA-seq. Target genes of differential exosomal miRNAs were identified using Targetscan and Miranda databases, followed by GO and KEGG enrichment analyses. Validation of key indicators of chondrocyte injury in KBD was conducted using Real-time quantitative PCR (RT-qPCR) and Immunohistochemical staining (IHC). A total of 20 exosomal miRNAs related to KBD were identified in serum, and 13 in chondrocytes (C28/I2). The identified exosomal miRNAs targeted 48,459 and 60,612 genes, primarily enriched in cell organelles and membranes, cell differentiation, and cytoskeleton in the serum, and the cytoplasm and nucleus, metal ion binding in chondrocyte (C28/I2). The results of the KEGG enrichment analysis indicated that the Ras signaling pathway may play a crucial role in the pathogenesis of KBD. Specifically, the upregulation of hsa-miR-181a-5p and hsa-miR-21-3p, along with the downregulation of hsa-miR-152-3p and hsa-miR-186-5p, were observed. Additionally, T-2 toxin intervention led to a significant downregulation of RALA, REL, and MAPK10 expression. Furthermore, the protein levels of RALA, REL, and MAPK10 were notably decreased in the superficial and middle layers of cartilage tissues from KBD. The induction of differential expression of chondrocyte exosomal miRNAs by T-2 toxin results in the collective regulation of target genes RALA, REL, and MAPK10, ultimately mediating the Ras signaling pathway and causing a disruption in chondrocyte extracellular matrix metabolism, leading to chondrocyte injury.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Toxina T-2 / Transducción de Señal / Condrocitos / MicroARNs / Exosomas Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Toxicology Año: 2024 Tipo del documento: Article Pais de publicación: Irlanda
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Toxina T-2 / Transducción de Señal / Condrocitos / MicroARNs / Exosomas Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Toxicology Año: 2024 Tipo del documento: Article Pais de publicación: Irlanda