Fig 2: PlGF with/without macrophage-depletion of VEGFR1 does not affect diabetes. (A) Schematic of a mouse model for DFD, in which C56/BL6 mice received STZ to induce diabetes and then a surgical ulcer at dorsal midline after one week. At the time of surgical ulcer induction, PlGF or saline was orthotopically injected biweekly while AAVs were given locally only once, immediately after ulcer induction. In another 4 weeks, the mice were sacrificed and analyzed. (B) Fasting blood glucose. (C) Representative immunofluorescent images for glucagon and insulin in mouse pancreas. (D) Beta-cell mass at sacrifice. *p < 0.05. NS, non-significant. Scale bars are 20 µm.

Fig 3: PlGF upregulates during foot wound healing and this upregulation is compromised in diabetes. (A) ELISA for PlGF in diseased foot tissue from a mouse model for DFD before induction of ulcer (day 0) and day 3 and day 7 after induction of DFD in mice. DU: diabetic ulcer. NDU: non-diabetic ulcer. (B, C) PlGF mRNA levels in diabetic foot skin (DS, equal to DU day 0) versus diabetic foot ulcer (NDU, equal to DU day 3) from human DFD dataset GSE134431 (B) and GSE80178 (C). (D) A hot map to show difference in gene expression from DS versus DU in GSE80178. (E) A pathway analysis to show difference in enriched pathway between DS and DU in GSE80178. *p < 0.05. NS, non-significant.

Fig 4: Macrophage-depletion of VEGF1R reduces macrophage number and reduces M2 polarization. (A) ELISA for PlGF levels in tissue from all experimental groups. (B) Representative flow charts for analysis and sorting for CD68 and CD163. (C, D) Quantification of CD68+ macrophage percentage (C) and CD163+ cells in total CD68+ cells (D). *p < 0.05. NS, non-significant.