Abstract: Objective: To explore the role and mechanism of Hypocrellin A (HA) in promoting apoptosis of Keloid fibroblasts (KFs) through reactive oxygen species (ROS)/c-Jun N-terminal kinase (JNK) pathway. Methods: KFs were primarily cultured and passaged. The 3rd generation KFs were divided into control group and different dose HA groups (0.125, 0.25, 0.5, 1.0 μmol/L HA treatment), HA+N-acetylcysteine (NAC) group (1.0 μmol/L HA+1.0 mmol/L NAC treatment). The optical density OD450 of cell proliferation, apoptosis rate, the contents of collagen metabolism indicators type I collagen (Col-I), α-smooth muscle actin(α-SMA), fibronectin (FN), oxidative stress indicators malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant capacity (T-AOC) and ROS, and the expression levels of endoplasmic reticulum stress markers GRP78, p-IRE-1 and p-JNK, cleaved caspase-3 in the ROS/JNK pathway were detected. Results: The OD450 level, the contents of Col-I α-SMA, FN, SOD, T-AOC in the control group were lower than those in the control group, while the apoptosis rate, the contents of MDA, ROS, and the expression levels of GRP78, p-IRE-1, p-JNK and cleared caspase-3 were higher than those in the control group (P<0.05). The higher the HA dose, the more significant the changes in the above indicators. The OD450 level, the contents of Col-I α-SMA, FN, SOD, T-AOC in the control group were lower than those in the HA+NAC group were higher than those in the 1.0 μmol/L HA group, while the apoptosis rate, the contents of MDA, ROS, and the expression levels of GRP78, p-IRE-1, p-JNK and cleared caspase-3 were lower than those in the 1.0 μmol/L HA group (P<0.05). Conclusion: HA promotes the apoptosis of KFs, which is related to the activation of ROS/JNK pathway mediated oxidative stress and endoplasmic reticulum stress.

Key words: keloid, fibroblasts, Hypocrellin A, apoptosis, reactive oxygen species, c-Jun N-terminal kinase