Related Experiment Video

Updated: Jun 6, 2026

Cholesterol Efflux Assay
07:54

Cholesterol Efflux Assay

Published on: March 6, 2012

MUC2 promotes cholesterol efflux in foam cells through ALKBH5-mediated m6A modification of ABCA1 mRNA

Pingping He1, Mao Peng2, Yifan Tang2

  • 1Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Health Science Center, Hunan Normal University, Changsha 410013, China; Aging Health Research Center, School of Nursing, Health Science Center, Hunan Normal University, Changsha 410013, China.

Clinica E Investigacion En Arteriosclerosis : Publicacion Oficial De La Sociedad Espanola De Arteriosclerosis
|June 4, 2026
PubMed
Abstract

Insights

Mucin 2 (MUC2) promotes cholesterol efflux and reduces foam cell formation in atherosclerosis. It achieves this by inhibiting ALKBH5, enhancing ABCA1 mRNA stability, and improving lipid metabolism.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Atherosclerosis involves lipid accumulation and foam cell formation.
  • Mucin 2 (MUC2), an intestinal protein, impacts lipid metabolism, but its role in atherosclerosis is not fully understood.
  • This study investigates MUC2's regulatory role in cholesterol efflux and foam cell development.

Purpose of the Study:

  • To elucidate the mechanism by which MUC2 regulates cholesterol efflux.
  • To determine MUC2's effect on foam cell formation in atherosclerosis.
  • To investigate the role of ALKBH5 and m6A modification in MUC2-mediated effects.

Main Methods:

  • THP-1 macrophage-derived foam cells were treated with MUC2.
  • ALKBH5 expression was manipulated using lentiviral vectors (knockdown and overexpression).
  • Lipid accumulation, cholesterol efflux, gene expression (ABCA1, ALKBH5), and m6A modification of ABCA1 mRNA were assessed.

Main Results:

  • MUC2 treatment increased ABCA1 expression, promoted cholesterol efflux, and decreased lipid accumulation in foam cells.
  • MUC2 inhibited the m6A demethylase ALKBH5, leading to increased m6A modification and stability of ABCA1 mRNA.
  • Silencing ALKBH5 mimicked MUC2's protective effects, while ALKBH5 overexpression reversed them.

Conclusions:

  • MUC2 inhibits foam cell formation and promotes cholesterol efflux in atherosclerosis.
  • This effect is mediated by MUC2's repression of ALKBH5, enhancing ABCA1 mRNA m6A modification and stability.
  • MUC2 represents a potential therapeutic target for atherosclerosis treatment.
Keywords:
ABCA1ALKBH5AterosclerosisAtherosclerosisMUC2Mucina 2m6A

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