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miR-125 regulates PI3K/Akt/mTOR signaling pathway in rheumatoid arthritis rats via PARP2

Kai Liu1, Yingang Zhang2, Liang Liu2

  • 1Department of Orthopedic, The First Affliated Hospital of Xi'an JiaoTong University, No. 277, Yanta West Road, Xi'an City, Shanxi Province 710061, China liukai244@163.com.

Bioscience Reports
|December 14, 2018
PubMed

Insights

MicroRNA-125 (miR-125) may reduce rheumatoid arthritis (RA) severity by inhibiting Poly(ADP-ribose) polymerase 2 (PARP2). This study shows miR-125 regulates the PI3K/Akt/mTOR pathway, offering a potential therapeutic target for RA.

Area of Science:

  • Immunology
  • Molecular Biology
  • Biochemistry

Background:

  • Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation and destruction.
  • The precise molecular mechanisms underlying RA pathogenesis are not fully understood, necessitating the identification of novel therapeutic targets.
  • MicroRNAs (miRNAs) have emerged as critical regulators in various biological processes, including inflammation and immune responses relevant to RA.

Purpose of the Study:

  • To investigate the role of miR-125 in the development of rheumatoid arthritis (RA).
  • To explore the potential of targeting miR-125 and its associated pathways for RA treatment.
  • To elucidate the molecular mechanism by which miR-125 influences RA pathogenesis, focusing on its interaction with PARP2.

Main Methods:

  • Establishment of a rat model of rheumatoid arthritis using Freund's Complete Adjuvant.
  • Assessment of clinical and pathological features including foot swelling, polyarthritis index, and spleen/thymus indices.
  • In vitro studies involving synovial cell culture, transfection with miR-125 mimics and PARP2-siRNA, and analysis using qRT-PCR, Western blot, luciferase reporter assay, ELISA, and MTT assay.

Main Results:

  • Rats in the RA model group exhibited significantly increased swelling, polyarthritis scores, and organ indices compared to controls.
  • Downregulation of miR-125 and upregulation of PARP2 were observed in the synovial tissues of RA model rats.
  • miR-125 directly inhibited PARP2 expression, and its mimics, combined with PARP2-siRNA, significantly reduced inflammatory markers (IL-1β, MMP-1) and suppressed the PI3K/Akt/mTOR signaling pathway.

Conclusions:

  • miR-125 plays a protective role in rheumatoid arthritis development.
  • PARP2 is a direct target of miR-125, and their interaction is crucial in modulating RA pathogenesis.
  • miR-125 may attenuate RA by inhibiting the PI3K/Akt/mTOR signaling pathway through direct suppression of PARP2, suggesting miR-125 as a potential therapeutic target for RA.
Keywords:
PARP2PI3K/Akt/mTOR signaling pathwaymiR-125rheumatoid arthritis

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