Macrophages regulate healing-associated fibroblasts in diabetic wound.
Mol Biol Rep
; 51(1): 203, 2024 Jan 25.
Article
in En
| MEDLINE
| ID: mdl-38270651
ABSTRACT
BACKGROUND:
Recovery from a foot ulcer is compromised in a diabetic status, due to the impaired tissue microenvironment that consists of altered inflammation, angiogenesis and fibrosis. Phenotypic alterations in both macrophages and fibroblasts have been detected in the diabetic wound. Recently, a fibroblast subpopulation that expresses high matrix metalloproteinase 1 (MMP1), MMP3, MMP11 and Chitinase-3-Like Protein 1 (CHI3L1) was associated with a successful diabetic wound healing. However, it is not known whether these healing-associated fibroblasts are regulated by macrophages. METHODS ANDRESULTS:
We used bioinformatic tools to analyze selected public databases on normal and diabetic skin from patients, and identified genes significantly altered in diabetes. In a mouse model for diabetic wound healing, we detected not only a loss of the spatiotemporal changes in interleukin 1ß (IL1ß), IL6, IL10 and vascular endothelial growth factor A (VEGF-A) in wound macrophages, but also a compromised expression of MMP1, MMP3, MMP11, CHI3L1 and VEGF-A in healing-associated wound fibroblasts in a diabetic status. Co-culture with diabetic macrophages significantly reduced the expression of MMP1, MMP3, MMP11, CHI3L1 and VEGF-A in fibroblasts from non-diabetic wound. Co-culture with non-diabetic macrophages or diabetic macrophages supplied with IL6 significantly increased the expression of MMP1, MMP3, MMP11, CHI3L1 and VEGF-A in fibroblasts from diabetic wound. Moreover, macrophage-specific expression of IL6 significantly improved wound healing and angiogenesis in diabetic mice.CONCLUSIONS:
Macrophages may induce the activation of wound-healing-associated fibroblasts, while the defective macrophages in diabetes may be corrected with IL6 treatment as a promising therapy for diabetic foot disease.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Vascular Endothelial Growth Factor A
/
Diabetes Mellitus, Experimental
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Mol Biol Rep
Year:
2024
Document type:
Article
Affiliation country: