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Author Spotlight: Isolation and Culture of Primary Synovial Macrophages and Fibroblasts from Murine Arthritis Tissue
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Inhibition of Aberrant Activated Fibroblast-Like Synoviocytes in Rheumatoid Arthritis by Leishmania Peptide via the

Jianling Su1,2, Xuemei Fan3, Yaoyao Zou2

  • 1Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510000, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|March 24, 2025
PubMed

Insights

The Leishmania-derived polypeptide LACK156-173 inhibits aggressive rheumatoid arthritis fibroblast-like synoviocytes by restoring fatty acid metabolism. This parasite-derived peptide offers potential therapeutic promise for rheumatoid arthritis.

Area of Science:

  • Immunology
  • Molecular Biology
  • Metabolic Disease

Background:

  • Fibroblast-like synoviocytes (FLSs) are key drivers of synovial invasion and joint destruction in rheumatoid arthritis (RA).
  • Dysregulated fatty acid metabolism, particularly fatty acid synthase (FASN) overexpression, contributes to the aggressive phenotype of RA-FLSs.

Purpose of the Study:

  • To investigate the therapeutic potential of the Leishmania homolog of receptors for activated C kinase (LACK)156-173 in rheumatoid arthritis.
  • To elucidate the mechanism by which LACK156-173 modulates RA-FLS behavior and metabolism.

Main Methods:

  • Analysis of RA-FLS phenotype and fatty acid metabolism.
  • Investigating the role of FASN, DRP1 phosphorylation, ROS production, and the PI3K/mTOR/NF-κB pathway.
  • Assessing the cellular uptake and target interaction of LACK156-173 via CAPN2-mediated endocytosis and FASN binding.

Main Results:

  • LACK156-173 inhibited the aggressive phenotype of RA-FLSs by restoring dysregulated fatty acid synthesis.
  • LACK156-173 directly binds to and inhibits FASN activity, reducing fatty acid accumulation.
  • This inhibition mitigated mitochondrial fragmentation, decreased ROS production, and modulated the PI3K/mTOR/NF-κB pathway.

Conclusions:

  • Restoring fatty acid metabolism is a viable strategy to alleviate synovial invasion and joint damage in RA.
  • LACK156-173 demonstrates therapeutic promise for rheumatoid arthritis by targeting FASN and normalizing cellular metabolism.
Keywords:
FASNLeishmania receptors for activated C kinasefatty acid synthesis metabolismfibroblast‐like synoviocytesrheumatoid arthritis

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