Integrated Skin Transcriptomics and Serum Multiplex Assays Reveal Novel Mechanisms of Wound Healing in Diabetic Foot Ulcers

Nonhealing diabetic foot ulcers (DFUs) are characterized by low-grade chronic inflammation, both locally and systemically. We prospectively followed a group of patients who either healed or developed nonhealing chronic DFUs. Serum and forearm skin analysis, both at the protein expression and the tra...

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Veröffentlicht in:Diabetes (New York, N.Y.) Jg. 69; H. 10; S. 2157
Hauptverfasser: Theocharidis, Georgios, Baltzis, Dimitrios, Roustit, Matthieu, Tellechea, Ana, Dangwal, Seema, Khetani, Radhika S, Shu, Bin, Zhao, Wanni, Fu, Jianfang, Bhasin, Swati, Kafanas, Antonios, Hui, Daniel, Sui, Shannan Ho, Patsopoulos, Nikolaos A, Bhasin, Manoj, Veves, Aristidis
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 01.10.2020
Schlagworte:
Adult
Aged
Aged, 80 and over
Cell Movement - genetics
Cell Movement - physiology
Cytochrome P-450 CYP1A1 - genetics
Cytochrome P-450 CYP1A1 - metabolism
Diabetic Foot - metabolism
Diabetic Foot - pathology
Humans
Middle Aged
Organic Anion Transporters - genetics
Organic Anion Transporters - metabolism
Sequence Analysis, RNA
Skin - metabolism
Skin - pathology
Transcriptome - genetics
Transcriptome - physiology
Vascular Endothelial Growth Factor A - metabolism
Wound Healing - genetics
Wound Healing - physiology
Young Adult
ISSN:1939-327X, 1939-327X
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Zusammenfassung:Nonhealing diabetic foot ulcers (DFUs) are characterized by low-grade chronic inflammation, both locally and systemically. We prospectively followed a group of patients who either healed or developed nonhealing chronic DFUs. Serum and forearm skin analysis, both at the protein expression and the transcriptomic level, indicated that increased expression of factors such as interferon-γ (IFN-γ), vascular endothelial growth factor, and soluble vascular cell adhesion molecule-1 were associated with DFU healing. Furthermore, foot skin single-cell RNA sequencing analysis showed multiple fibroblast cell clusters and increased inflammation in the dorsal skin of patients with diabetes mellitus (DM) and DFU specimens compared with control subjects. In addition, in myeloid cell DM and DFU upstream regulator analysis, we observed inhibition of interleukin-13 and IFN-γ and dysregulation of biological processes that included cell movement of monocytes, migration of dendritic cells, and chemotaxis of antigen-presenting cells pointing to an impaired migratory profile of immune cells in DM skin. The and genes, which were upregulated at the forearm of nonhealers, were mainly expressed by the vascular endothelial cell cluster almost exclusively in DFU, indicating a potential important role in wound healing. These results from integrated protein and transcriptome analyses identified individual genes and pathways that can potentially be targeted for enhancing DFU healing.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
ISSN:1939-327X
1939-327X
DOI:10.2337/db20-0188