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. 2020 Sep 16;11:4678. doi: 10.1038/s41467-020-18276-0

Fig. 3. Upstream regulators involved in promoting proliferation and cell survival of immune cells are inhibited in DFUs and activated in oral and skin acute wounds.

Fig. 3

a Top upstream regulators enriched in oral D3/D1 vs. skin D3/D1 vs. DFU/DFS. b Upstream regulators found to be activated in oral and skin wounds that are suppressed or partially regulated in DFUs involved in proliferation, inflammatory response, leukocyte migration and proliferation of leukocytes. NA non applicable. c FOXM1 predicted network shows activation of proliferation and inflammatory response in oral and skin wounds compared to suppression in DFUs. d qPCR validations of upstream regulators FOXM1, STAT3, and TNFα confirms suppression in DFUs compared to activation in oral and skin human wounds. n = 2 biologically independent samples for oral and skin wounds; n = 3 biologically independent samples for DFUs. Data presented as mean ± SD. FOXM1 P-values oral D3/D1 vs DFU/DFS: **P = 0.0095; FOXM1 P-values skin D3/D1 vs DFU/DFS: **P = 0.008; STAT3 P-values oral D3/D1 vs DFU/DFS: **P = 0.003; STAT3 P-values skin D3/D1 vs DFU/DFS: **P = 0.0034; TNF P-values oral D3/D1 vs DFU/DFS: **P = 0.0041; TNF P-values skin D3/D1 vs DFU/DFS: *P = 0.0436 (two-way ANOVA followed by Tukey’s post hoc test). e Immunostaining of FOXM1 (green immunofluorescence signal) and keratin 5 (K5, in red) in oral and skin day 3 wounds and DFUs. Robust staining of FOXM1 found in oral and acute skin wounds but is absent in DFUs. Stainings were performed once with three biologically independent patient samples per group. Scale bar = 100 µm.