Related Experiment Video
Updated: Aug 3, 2025
Investigation of Macrophage Polarization Using Bone Marrow Derived Macrophages
Published on: June 23, 2013
HnRNPA2B1 Aggravates Inflammation by Promoting M1 Macrophage Polarization
Meiyao Meng1, Yuxiang Cao1, Yankang Zhang1
1Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
Abstract:
Macrophages have critical contributions to both acute and chronic inflammatory diseases, for example, bowel disease and obesity, respectively. However, little is known about the post-transcriptional regulatory mechanisms in macrophage-mediated inflammatory diseases. hnRNPA2B1 (A2B1) is an RNA binding protein for mRNA fate determination. We showed that hnRNPA2B1 mRNA levels were increased in colon in dextran sodium sulfate (DSS)-induced colitis mice and in epididymal white adipose tissue (eWAT) and spleen of high-fat-diet (HFD)-induced obese mice. Consistently, mice with haploinsufficiency of A2B1 (A2B1 HET) are protected against DSS-induced acute colitis and HFD-induced obesity, with decreased M1 macrophages polarization in colon, eWAT and spleen. Mechanistically, A2B1 mRNA and protein levels were increased in LPS-stimulated RAW 264.7 macrophages, and A2B1 enhanced RNA stability of pro-inflammatory genes Tnfα, Il-6 and Il-1β for the regulation of macrophages polarization. Interestingly, A2B1 HET mice exhibited reduced white fat expansion, which was influenced by macrophages, since conditioned medium from macrophages with A2B1 manipulation significantly changed preadipocyte proliferation. Our data demonstrate that A2B1 plays a vital role in macrophage-mediated inflammation via regulating mRNA stability, suggesting that A2B1 may be served as a promising target for the intervention of acute and chronic inflammatory diseases.
Insights
The RNA binding protein hnRNPA2B1 (A2B1) promotes inflammation in macrophages by stabilizing pro-inflammatory mRNAs. Reducing A2B1 levels protects against inflammatory diseases like colitis and obesity.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Macrophages are key players in acute and chronic inflammatory diseases, including inflammatory bowel disease and obesity.
- Post-transcriptional regulation mechanisms in macrophage-mediated inflammation are not well understood.
- Heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1 or A2B1) is an RNA-binding protein involved in mRNA regulation.
Purpose of the Study:
- To investigate the role of hnRNPA2B1 in macrophage-mediated inflammatory diseases.
- To elucidate the mechanisms by which hnRNPA2B1 regulates macrophage polarization and inflammatory responses.
- To assess the therapeutic potential of targeting hnRNPA2B1 for inflammatory conditions.
Main Methods:
- Examined hnRNPA2B1 mRNA and protein levels in mouse models of colitis and obesity (DSS and HFD, respectively).
- Utilized hnRNPA2B1 haploinsufficiency (A2B1 HET) mouse models to assess protection against inflammation.
- Investigated hnRNPA2B1's effect on pro-inflammatory gene mRNA stability (Tnfα, Il-6, Il-1β) in LPS-stimulated macrophages.
- Assessed the impact of macrophage-derived factors on preadipocyte proliferation in vitro.
Main Results:
- hnRNPA2B1 expression was upregulated in inflammatory conditions (colitis, obesity).
- A2B1 HET mice showed protection against DSS-induced colitis and HFD-induced obesity, with reduced M1 macrophage polarization.
- hnRNPA2B1 enhanced the stability of pro-inflammatory cytokine mRNAs (Tnfα, Il-6, Il-1β), promoting M1 polarization.
- hnRNPA2B1 manipulation in macrophages affected preadipocyte proliferation, influencing white fat expansion.
Conclusions:
- hnRNPA2B1 plays a critical role in macrophage-mediated inflammation by regulating mRNA stability.
- Targeting hnRNPA2B1 offers a potential therapeutic strategy for acute and chronic inflammatory diseases.
- hnRNPA2B1 influences macrophage polarization and adipose tissue expansion, highlighting its broader role in metabolic inflammation.
More Related Videos
07:45Metabolic Characterization of Polarized M1 and M2 Bone Marrow-derived Macrophages Using Real-time Extracellular Flux Analysis
Published on: November 28, 2015
10:43Polarization of M1 and M2 Human Monocyte-Derived Cells and Analysis with Flow Cytometry upon Mycobacterium tuberculosis Infection
Published on: September 18, 2020
Related Concept Videos
01:38Inflammation
02:26NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...