Prostaglandin F2 Alpha Protects Against Pericyte Apoptosis By Inhibiting The Pi3k/Akt/Gsk3 Beta/Beta-Catenin Signaling Pathway

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 F2 alpha (PGF2 alpha) 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 PGF2 alpha on pericyte apoptosis has yet to be described.Methods: Two animal models were constructed: a high-fat diet (HFD) and streptozotocin (STZ)induced type 2 diabetes mouse model and a spontaneous type 2 diabetes db/db mouse model. We analyzed pathological changes, and performed TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) staining and western blot to detect apoptosis in the retinas of diabetic mice. For our in vitro experiments, we selected human retinal pericytes and subjected them to high-glucose (HG), PGF2 alpha, and AL8810 (an antagonist of the PGF2 alpha receptor) treatment. Subsequently, apoptosis and the levels of PI3K/ Akt/GSK3 beta/beta-catenin pathway-related proteins were detected by TUNEL staining and western blot, respectively.Results: The levels of apoptosis were increased in the retinas of diabetic mice in both T2DM models. In vitro, HG treatment increased apoptosis and inhibited PI3K/Akt/GSK3 beta/beta-catenin signaling in pericytes. In contrast, PGF2 alpha treatment inhibited pericyte apoptosis while increasing the levels of the PI3K, p-Akt/t-Akt, p-GSK3 beta/t-GSK3 beta, and beta-catenin proteins; however, these PGF2 alpha-induced effects were eliminated by ALL80.Conclusions: PGF2 alpha may make a key contribution to reducing pericyte apoptosis and protecting against DR via its inhibition of the PI3K/Akt/GSK3 beta/beta-catenin signaling pathway.