Figure 7

Combined rhFGF4 and rhVEGF-A treatment improves high glucose-impaired biological properties of diabetic mouse dermal fibroblasts. Functional in vitro tests with age- and passage-matched fibroblasts isolated from the skin of diabetic and wild-type mice: (A) Proliferation after 24 hours of culture. Diabetic fibroblasts cultured in 5.5 mM glucose DMEM (empty bars) show impaired basal proliferation in comparison to wild-type fibroblasts (black bars) which is even more intense when the db/db cells are kept in 25 mM glucose (gray bars). rhFGF4 (delivered alone or in combination with rhVEGF-A) induces WT cell proliferation whereas only co-stimulation with rhVEGF-A significantly increases proliferation of cells isolated from db/db mice and cultured in 5.5 mM glucose (similar tendency in diabetic fibroblasts kept in 25 mM glucose). (B) Migration after 20 hours of culture. Diabetic fibroblasts cultured in 5.5 mM glucose DMEM (empty bars) show impaired basal migration on gelatin/fibronectin in comparison to wild-type fibroblasts (black bars) which is even more intense when the cells are kept in 25 mM glucose (gray bars). Migration towards rhFGF4 gradient (delivered alone or in combination with rhVEGF-A) is preserved in WT cells and in cells from db/db mice cultured in 5.5 mM glucose. Fibroblasts isolated from the skin of db/db mice and cultured in 25 mM glucose show impaired migration towards rhFGF4, that can be restored by combined rhFGF4 and rhVEGF-A treatment. C - control, V - rhVEGF-A (50 ng ml^-1), F - rhFGF4 (50 ng ml^-1), V+F - rhVEGF-A (50 ng ml^-1) and rhFGF4 (50 ng ml^-1). Graphs represent means ± SEM from n = 5 (A) and n = 3 (B) independent experiments performed in duplicates; *p < 0.05 vs appropriate control; # p < 0.05 vs WT control; § p < 0.05 vs WT and db/db 5.5 mM control.