Fig. 3

Histidine-pyridine-histidine ligand derivative HPH-15 treatment ameliorates bleomycin (BLM)-induced skin fibrosis in mice. The antifibrotic effects of HPH-15 were analyzed at the endpoint of the preventive model (a–c) and curative model (d and e). The preventive model was performed by daily subcutaneous injections of BLM into the back skin of the mice concurrently with daily oral gavage of HPH-15 or vehicle (sterilized olive oil) for 4 weeks. In the curative model, BLM was administered on alternate days for 6 weeks. Two weeks after the first injection, mice were given a daily dose of HPH-15 or vehicle for the remaining 4 weeks. Representative images of H&E-stained (upper pictures) and Masson’s trichrome-stained (lower pictures) tissue. Arrows indicate dermal thickness. Scale bar = 100 μm. Skin fibrosis was compared by determining dermal thickness, ratio of trichrome area/total area, and soluble collagen content. All values represent mean ± SEM; n = 4–6 per group. * p ≤ 0.05; ** p ≤ 0.01