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Macrophage-derived mir-100-5p orchestrates synovial proliferation and inflammation in rheumatoid arthritis through

Huan Liu1, Yuehong Chen1, Yupeng Huang2

  • 1Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, 610041, China.

Journal of Nanobiotechnology
|April 21, 2024
PubMed
Abstract

Insights

Macrophages exacerbate rheumatoid arthritis (RA) by sending extracellular vesicles (sEVs) with low miR-100-5p to RA cells, promoting inflammation and proliferation via the mTOR pathway, offering new therapeutic targets.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Rheumatoid arthritis (RA) is a chronic autoimmune disease causing joint inflammation and disability.
  • Macrophages are key regulators of RA inflammation, but their role in RA-fibroblast-like synoviocyte (RA-FLS) proliferation and inflammation is not fully understood.
  • Extracellular vesicles (sEVs) and microRNAs (miRNAs) are implicated in intercellular communication within the RA microenvironment.

Purpose of the Study:

  • To investigate the role of macrophage-derived extracellular vesicles (sEVs) in regulating RA-FLS proliferation and inflammation.
  • To elucidate the specific molecular mechanisms, including the miR-100-5p/mTOR axis, involved in this process.

Main Methods:

  • Isolation and characterization of sEVs from bone marrow-derived macrophages (BMDM) of collagen-induced arthritis (CIA) mice and normal mice.
  • Assessment of RA-FLS proliferation and inflammatory responses upon treatment with BMDM-sEVs.
  • Quantification of miR-100-5p levels in sEVs and analysis of its regulatory role in RA-FLS via the mTOR pathway.

Main Results:

  • Macrophage-derived sEVs from arthritic mice (cBMDM-sEVs) were more abundant and induced significant RA-FLS proliferation and inflammation compared to those from normal mice (nBMDM-sEVs).
  • cBMDM-sEVs showed decreased levels of miR-100-5p.
  • Overexpression of miR-100-5p in RA-FLS counteracted the proliferative and inflammatory effects induced by cBMDM-sEVs by targeting the mammalian target of rapamycin (mTOR) pathway.

Conclusions:

  • Macrophages contribute to RA pathogenesis by transferring miR-100-5p-deficient sEVs to RA-FLS, promoting disease progression.
  • The miR-100-5p/mTOR axis is a critical mediator of macrophage-induced RA-FLS activation.
  • These findings highlight novel mechanisms in RA and identify potential therapeutic targets for RA intervention.
Keywords:
Extracellular vesiclesMacrophagesRheumatoid arthritismTORmiR-100-5p

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