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- Title
Integrated Skin Transcriptomics and Serum Multiplex Assays Reveal Novel Mechanisms of Wound Healing in Diabetic Foot Ulcers.
- Authors
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
- Abstract
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 SLCO2A1 and CYP1A1 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.
- Subjects
DIABETIC foot; WOUND healing; ANTIGEN presenting cells; VASCULAR endothelial cells; CELL migration; PROTEIN metabolism; PROTEINS; RESEARCH; SEQUENCE analysis; SKIN; RESEARCH methodology; EVALUATION research; MEDICAL cooperation; CELL motility; COMPARATIVE studies; GENE expression profiling; RESEARCH funding; OXIDOREDUCTASES; VASCULAR endothelial growth factors
- Publication
Diabetes, 2020, Vol 69, Issue 10, p2157
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db20-0188