The Histone Methyltransferase, MLL1, Directs Macrophage-Mediated Inflammation in Wound Healing and is Altered in a Murine Model of Obesity and Type 2 Diabetes
Macrophages are critical for the initiation and resolution of the inflammatory phase of wound repair. In diabetes, macrophages display a prolonged inflammatory phenotype in late wound healing. Recently, Mixed-Lineage Leukemia-1 (MLL1) has been shown to direct gene expression by regulating NFκB-mediated inflammatory gene transcription. Thus, we hypothesized that MLL1 influences macrophage-mediated inflammation in wound repair. We utilized a myeloid-specific Mll1 knockout(Mll1(f/f)Lyz2(Cre+) ) to determine the function of MLL1 in wound healing. Mll1(f/f)Lyz2(Cre+) mice display delayed wound healing and decreased wound macrophage inflammatory cytokine production compared to controls. Further, wound macrophages from Mll1(f/f)Lyz2(Cre+) mice demonstrated decreased Histone-3 Lysine-4 trimethylation (H3K4me3; activation mark) at NFκB-binding sites on inflammatory gene promoters. Interestingly, early wound macrophages from 'pre-diabetic' mice displayed similarly decreased MLL1, H3K4me3 at inflammatory gene promoters, and inflammatory cytokines compared to controls. Importantly, late wound macrophages from 'pre-diabetic' mice demonstrated an increase in MLL1, H3K4me3 at inflammatory gene promoters, and inflammatory cytokines. 'Pre-diabetic' macrophages treated with an MLL1 inhibitor demonstrated reduced inflammation. Finally, monocytes from type-2 diabetic(T2D) patients had increased Mll1 compared to non-diabetic controls. These results define an important role for MLL1 in regulating macrophage-mediated inflammation in wound repair and identify a potential target for the treatment of chronic inflammation in diabetic wounds.
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 September 2021.
All research outputs
#7,532,940
of 22,985,065 outputs
Outputs from Diabetes
#4,090
of 9,271 outputs
Outputs of similar age
#120,310
of 315,315 outputs
Outputs of similar age from Diabetes
#53
of 84 outputs
Altmetric has tracked 22,985,065 research outputs across all sources so far. This one is in the 44th percentile – i.e., 44% of other outputs scored the same or lower than it.
So far Altmetric has tracked 9,271 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.2. This one is in the 28th percentile – i.e., 28% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 315,315 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 54% of its contemporaries.
We're also able to compare this research output to 84 others from the same source and published within six weeks on either side of this one. This one is in the 34th percentile – i.e., 34% of its contemporaries scored the same or lower than it.
