Metabolic Enzyme Triosephosphate Isomerase 1 and Nicotinamide Phosphoribosyltransferase, Two Independent Inflammatory

Ming Lei1, Meng-Qing Tao1,2, Yi-Jin Wu1,2

  • 1Xin'an Medicine Research Center, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital), Wuhu, China.

Frontiers in Immunology
|February 3, 2022
PubMed

Insights

Metabolic regulators NAMPT and TPI1 drive inflammation in rheumatoid arthritis (RA). Targeting these pathways, particularly TPI1 and its interaction with HIF-1α, offers novel anti-rheumatic strategies.

Area of Science:

  • Immunometabolism
  • Rheumatoid Arthritis Pathogenesis
  • Molecular Biology

Background:

  • Metabolic intervention is a promising anti-rheumatic approach.
  • NAMPT is a known therapeutic target in rheumatoid arthritis (RA).
  • Other metabolic regulators involved in RA inflammation remain under investigation.

Purpose of the Study:

  • To investigate metabolic regulators coordinating with NAMPT in rheumatoid arthritis (RA).
  • To explore the role of TPI1 and its interaction with HIF-1α in RA.
  • To stratify RA patients based on gene expression and compare clinical manifestations.

Main Methods:

  • Monitoring of Nampt and inflammatory indicators in collagen-induced arthritis (CIA) rat models.
  • RNA-sequencing to compare gene expression in Nampt-expressing CIA rat samples.
  • Validation in human subjects and patient stratification based on gene expression differences.

Main Results:

  • Nampt overexpression correlated with early-stage CIA and upregulation of iNos and Il-1β.
  • TPI1, a glycolytic enzyme, showed sustained expression changes in CIA rats and elevated levels in RA patients.
  • TPI1 expression correlated with inflammatory monocyte markers and reciprocal interaction with HIF-1α was observed.

Conclusions:

  • Both NAMPT and TPI1 contribute to monocyte-mediated inflammation in RA, despite dominating different disease stages.
  • TPI1, regulated by HIF-1α, plays a significant role in RA pathogenesis.
  • Understanding these metabolic pathways offers potential for novel anti-rheumatic therapies.

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