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Download fileIntegrated skin transcriptomics and serum multiplex assays reveal novel mechanisms of wound healing in diabetic foot ulcers
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posted on 2020-08-06, 16:30 authored by Ada AdminAda Admin, Georgios Theocharidis, Dimitrios Baltzis, Matthieu Roustit, Ana Tellechea, Seema Dangwal, Radhika S. Khetani, Bin Shu, Wanni Zhao, Jianfang Fu, Swati Bhasin, Antonios Kafanas, Daniel Hui, Shannan Ho Sui, Nikolaos A. Patsopoulos, Manoj Bhasin, Aristidis VevesNon-healing diabetic foot ulceration (DFU) is characterized by low grade
chronic inflammation, both locally and systemically. We prospectively followed
a group of DFU patients who either healed or developed non-healing chronic DFU.
Serum and forearm skin analysis, both at protein expression and transcriptomic
level, indicated that increased expression of factors such as IFNγ, VEGF and sVCAM-1 were
associated with DFU healing. Furthermore, foot skin single-cell RNA-seq
analysis showed multiple fibroblast cell clusters and increased inflammation in
the dorsal skin of Diabetes Mellitus (DM) patients and DFU specimens when
compared to controls. In addition, in myeloid cells of DM and DFU patients
upstream regulator analysis, we observed inhibition of IL-13 and IFNγ 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 diabetic skin. The SLCO2A1 and CYP1A1 genes,
which were up-regulated at the forearm of Non-Healers, 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