Prostaglandin F2α protects against pericyte apoptosis by inhibiting the PI3K/Akt/GSK3β/β-catenin signaling pathway
Ying Cheng, Liyuan Peng, X.Q. Deng, Ting Li, Hang Guo, Chaofei Xu, Ting Fang, Xiaohuan Liu, Bei Sun, Liming Chen
Abstract
BACKGROUND: Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and the main cause of non-traumatic blindness in adults. Pericyte loss is known to be an early pathological change of DR. Our group's previous research indicated that prostaglandin F2α (PGF2α) acts as an eicosanoidal protector against non-proliferative DR that can regulate the mobility of pericytes in a RhoA-mediated manner. However, the effect of PGF2α on pericyte apoptosis has yet to be described. METHODS: experiments, we selected human retinal pericytes and subjected them to high-glucose (HG), PGF2α, and AL8810 (an antagonist of the PGF2α receptor) treatment. Subsequently, apoptosis and the levels of PI3K/Akt/GSK3β/β-catenin pathway-related proteins were detected by TUNEL staining and western blot, respectively. RESULTS: , HG treatment increased apoptosis and inhibited PI3K/Akt/GSK3β/β-catenin signaling in pericytes. In contrast, PGF2α treatment inhibited pericyte apoptosis while increasing the levels of the PI3K, p-Akt/t-Akt, p-GSK3β/t-GSK3β, and β-catenin proteins; however, these PGF2α-induced effects were eliminated by ALL80. CONCLUSIONS: PGF2α may make a key contribution to reducing pericyte apoptosis and protecting against DR via its inhibition of the PI3K/Akt/GSK3β/β-catenin signaling pathway.