Back to Search
Start Over
Macrophage LMO7 deficiency facilitates inflammatory injury via metabolic-epigenetic reprogramming
- Source :
- Acta Pharmaceutica Sinica B, Vol 13, Iss 12, Pp 4785-4800 (2023)
- Publication Year :
- 2023
- Publisher :
- Elsevier, 2023.
-
Abstract
- Inflammatory bowel disease (IBD) is a formidable disease due to its complex pathogenesis. Macrophages, as a major immune cell population in IBD, are crucial for gut homeostasis. However, it is still unveiled how macrophages modulate IBD. Here, we found that LIM domain only 7 (LMO7) was downregulated in pro-inflammatory macrophages, and that LMO7 directly degraded 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) through K48-mediated ubiquitination in macrophages. As an enzyme that regulates glycolysis, PFKFB3 degradation led to the glycolytic process inhibition in macrophages, which in turn inhibited macrophage activation and ultimately attenuated murine colitis. Moreover, we demonstrated that PFKFB3 was required for histone demethylase Jumonji domain-containing protein 3 (JMJD3) expression, thereby inhibiting the protein level of trimethylation of histone H3 on lysine 27 (H3K27me3). Overall, our results indicated the LMO7/PFKFB3/JMJD3 axis is essential for modulating macrophage function and IBD pathogenesis. Targeting LMO7 or macrophage metabolism could potentially be an effective strategy for treating inflammatory diseases.
Details
- Language :
- English
- ISSN :
- 22113835
- Volume :
- 13
- Issue :
- 12
- Database :
- Directory of Open Access Journals
- Journal :
- Acta Pharmaceutica Sinica B
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.114ace64ac45f0afcb9909473a3cb2
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.apsb.2023.09.012