@article {1574693,
	title = {Integrated Skin Transcriptomics and Serum Multiplex Assays Reveal Novel Mechanisms of Wound Healing in Diabetic Foot Ulcers},
	journal = {Diabetes},
	volume = {69},
	number = {10},
	year = {2020},
	month = {2020 10},
	pages = {2157-2169},
	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  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.},
	keywords = {Adult, Aged, Aged, 80 and over, Cell Movement, Cytochrome P-450 CYP1A1, Diabetic Foot, Humans, Middle Aged, Organic Anion Transporters, Sequence Analysis, RNA, Skin, Transcriptome, Vascular Endothelial Growth Factor A, Wound Healing, Young Adult},
	issn = {1939-327X},
	doi = {10.2337/db20-0188},
	author = {Theocharidis, Georgios and Baltzis, Dimitrios and Roustit, Matthieu and Tellechea, Ana and Dangwal, Seema and Khetani, Radhika S and Shu, Bin and Zhao, Wanni and Fu, Jianfang and Bhasin, Swati and Kafanas, Antonios and Hui, Daniel and Ho Sui, Shannan and Patsopoulos, Nikolaos A and Bhasin, Manoj and Veves, Aristidis}
}
