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MicroRNA-218 alleviates sepsis inflammation by negatively regulating VOPP1 via JAK/STAT pathway.

Abstract

OBJECTIVE

To investigate the possible role of microRNA-218 in the pathogenesis of sepsis and its underlying mechanism.

PATIENTS AND METHODS

MicroRNA-218 expression in peripheral blood mononuclear cells (PBMCs) of 53 sepsis patients and 20 healthy controls was detected by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). MicroRNA-218 expression in Treg cells of sepsis patients and healthy controls was also detected. The binding condition of microRNA-218 to VOPP1 was confirmed by dual-luciferase reporter gene assay and RNA binding protein immunoprecipitation (RIP) assay, respectively. Furthermore, sepsis mouse model was constructed. MicroRNA-218 mimics or inhibitor was injected into mouse tail vein, respectively. The proportion of Treg cells was compared between sepsis mice injected with microRNA-218 mimics and inhibitor. Expressions of microRNA-218 and VOPP1 in Treg cells extracted from sepsis mouse were detected. ELISA (enzyme-linked immunosorbent assay) assay was conducted to detect serum levels of inflammatory factors (TNF-α, IL-6, TGF-β, and IL-10) in sepsis mouse. Finally, protein expressions of key genes in JAK/STAT pathway in sepsis mouse spleen were detected by Western blot.

RESULTS

MicroRNA-218 expression in sepsis patients was remarkably lower than that of healthy controls, which was gradually decreased with the deteriorating symptoms. Specifically, microRNA-218 expression was the lowest in patients who died of sepsis. Downregulated microRNA-218 was seen in Treg cells extracted from advanced sepsis patients. Both dual-luciferase reporter gene assay and RIP assay suggested that microRNA-218 can bind to VOPP1. VOPP1 expression was negatively regulated by microRNA-218. In advanced sepsis mouse, administration of microRNA-218 mimics increased expressions of TNF-α and IL-6, but decreased expressions of IL-10 and TGF-β. Western blot results indicated that microRNA-218 can inhibit the JAK/STAT pathway in sepsis mice.

CONCLUSIONS

MicroRNA-218 expression in the PBMCs of sepsis patients was remarkably reduced, which inhibited sepsis development via negatively regulating VOPP1 and suppressing JAK/STAT pathway.

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  • Authors+Show Affiliations

    ,

    Department of Critical Care Medicine, Dezhou People's Hospital, Dezhou, China. 465786439@qq.com.

    ,

    Source

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    30229837

    Citation

    Li, J-M, et al. "MicroRNA-218 Alleviates Sepsis Inflammation By Negatively Regulating VOPP1 Via JAK/STAT Pathway." European Review for Medical and Pharmacological Sciences, vol. 22, no. 17, 2018, pp. 5620-5626.
    Li JM, Zhang H, Zuo YJ. MicroRNA-218 alleviates sepsis inflammation by negatively regulating VOPP1 via JAK/STAT pathway. Eur Rev Med Pharmacol Sci. 2018;22(17):5620-5626.
    Li, J. M., Zhang, H., & Zuo, Y. J. (2018). MicroRNA-218 alleviates sepsis inflammation by negatively regulating VOPP1 via JAK/STAT pathway. European Review for Medical and Pharmacological Sciences, 22(17), pp. 5620-5626. doi:10.26355/eurrev_201809_15827.
    Li JM, Zhang H, Zuo YJ. MicroRNA-218 Alleviates Sepsis Inflammation By Negatively Regulating VOPP1 Via JAK/STAT Pathway. Eur Rev Med Pharmacol Sci. 2018;22(17):5620-5626. PubMed PMID: 30229837.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - MicroRNA-218 alleviates sepsis inflammation by negatively regulating VOPP1 via JAK/STAT pathway. AU - Li,J-M, AU - Zhang,H, AU - Zuo,Y-J, PY - 2018/9/20/entrez PY - 2018/9/20/pubmed PY - 2018/9/20/medline SP - 5620 EP - 5626 JF - European review for medical and pharmacological sciences JO - Eur Rev Med Pharmacol Sci VL - 22 IS - 17 N2 - OBJECTIVE: To investigate the possible role of microRNA-218 in the pathogenesis of sepsis and its underlying mechanism. PATIENTS AND METHODS: MicroRNA-218 expression in peripheral blood mononuclear cells (PBMCs) of 53 sepsis patients and 20 healthy controls was detected by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). MicroRNA-218 expression in Treg cells of sepsis patients and healthy controls was also detected. The binding condition of microRNA-218 to VOPP1 was confirmed by dual-luciferase reporter gene assay and RNA binding protein immunoprecipitation (RIP) assay, respectively. Furthermore, sepsis mouse model was constructed. MicroRNA-218 mimics or inhibitor was injected into mouse tail vein, respectively. The proportion of Treg cells was compared between sepsis mice injected with microRNA-218 mimics and inhibitor. Expressions of microRNA-218 and VOPP1 in Treg cells extracted from sepsis mouse were detected. ELISA (enzyme-linked immunosorbent assay) assay was conducted to detect serum levels of inflammatory factors (TNF-α, IL-6, TGF-β, and IL-10) in sepsis mouse. Finally, protein expressions of key genes in JAK/STAT pathway in sepsis mouse spleen were detected by Western blot. RESULTS: MicroRNA-218 expression in sepsis patients was remarkably lower than that of healthy controls, which was gradually decreased with the deteriorating symptoms. Specifically, microRNA-218 expression was the lowest in patients who died of sepsis. Downregulated microRNA-218 was seen in Treg cells extracted from advanced sepsis patients. Both dual-luciferase reporter gene assay and RIP assay suggested that microRNA-218 can bind to VOPP1. VOPP1 expression was negatively regulated by microRNA-218. In advanced sepsis mouse, administration of microRNA-218 mimics increased expressions of TNF-α and IL-6, but decreased expressions of IL-10 and TGF-β. Western blot results indicated that microRNA-218 can inhibit the JAK/STAT pathway in sepsis mice. CONCLUSIONS: MicroRNA-218 expression in the PBMCs of sepsis patients was remarkably reduced, which inhibited sepsis development via negatively regulating VOPP1 and suppressing JAK/STAT pathway. SN - 2284-0729 UR - https://www.unboundmedicine.com/medline/citation/30229837/MicroRNA_218_alleviates_sepsis_inflammation_by_negatively_regulating_VOPP1_via_JAK/STAT_pathway_ L2 - https://www.europeanreview.org/article/15827 DB - PRIME DP - Unbound Medicine ER -