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Updated: Jun 22, 2026
10:07
Investigation of Macrophage Polarization Using Bone Marrow Derived Macrophages
Published on: June 23, 2013
Peroxisome proliferator-activated receptor alpha (PPARalpha) agonists down-regulate alpha2-macroglobulin expression
María del Carmen González1, J Christopher Corton, Russell C Cattley
1Universidad San Pablo-CEU, Madrid, Spain.
Biochimie
|June 6, 2009
Summary
Fenofibrate and WY-14,643, PPARalpha agonists, reduce alpha2-macroglobulin (A2Mg) expression in rats and mice. This study identifies A2Mg as a novel PPARalpha agonist-regulated gene.
Area of Science:
- Pharmacology
- Molecular Biology
- Biochemistry
Background:
- Fibrates are PPARalpha ligands influencing lipid, glucose, and inflammatory parameters.
- The acute-phase response (APR) involves inflammatory proteins like alpha2-macroglobulin (A2Mg).
- A2Mg levels are low in normal rats but high in pregnant rats.
Purpose of the Study:
- To investigate the effect of fenofibrate on hepatic A2Mg expression in pregnant and virgin rats.
- To determine if PPARalpha mediates fibrate effects on A2Mg and other APR genes.
- To identify A2Mg as a novel PPARalpha agonist-regulated gene.
Main Methods:
- Reverse transcription-polymerase chain reaction (RT-PCR) and Northern blot analysis.
- Treatment of pregnant and virgin rats with fenofibrate.
- Treatment of wild-type and PPARalpha-null mice with WY-14,643 (WY) or di-2-ethylhexyl phthalate (DEHP).
Main Results:
- Fenofibrate decreased A2Mg expression in both virgin and pregnant rats, with a sharper decrease in pregnant rats.
- WY-14,643, but not DEHP, reduced A2Mg and gamma-fibrinogen (gamma-Fib) expression in wild-type mice, but not in PPARalpha-null mice.
- Fenofibrate and WY-14,643 modulated A2Mg expression in rats and mice under both basal and augmented conditions.
Conclusions:
- PPARalpha agonists, including fenofibrate and WY-14,643, regulate A2Mg expression.
- A2Mg is identified as a novel gene directly regulated by PPARalpha agonists.
- These findings contribute to understanding the role of PPARalpha in regulating inflammatory and acute-phase proteins.
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