Allogeneic platelet-rich plasma inhibits ferroptosis in promoting wound repair of type 2 diabetic ulcers

Free Radic Biol Med. 2024 Feb 24:S0891-5849(24)00102-3. doi: 10.1016/j.freeradbiomed.2024.02.020. Online ahead of print.ABSTRACTIncreasing evidence has revealed the emerging role of ferroptosis in the pathophysiology of type 2 diabetes mellitus (T2DM) and its complications. Platelet-rich plasma (PRP) has been demonstrated to facilitate the healing of T2DM ulcers. However, the mechanism by which PRP repairs T2DM ulcers remains unclear. Here, we sought to investigate the interaction between PRP and ferroptosis in repairing T2DM ulcers. The results showed that the cellular activity, proliferation, and migration of fibroblasts were down-regulated, and the cellular activity and normal function of vascular endothelial cells were impaired in the high glucose environment or under RSL3 conditions (a GSH peroxidase 4 inhibitor and ferroptosis inducer). Additionally, both cells experienced over-activation of multiple forms of reactive oxygen species (ROS) and lipid peroxidation. In the T2DM rat model, we observed a decreased rate of ulcer wound healing, impaired proliferative capacity, diminished vascular regeneration, and marked inflammation and hyperfibrosis. More importantly, there was typical damage to mitochondria, increased levels of iron ions, and consistent alterations in protein expression of ferroptosis-related factors. These factors include cyclooxygenase-2 (COX2), glutathione peroxidase 4 (GPX4), transferrin receptor (TFRC), and Solute Carrier Family 7 Member 11 (SLC7A11), a...
Source: Free Radical Biology and Medicine - Category: Biology Authors: Source Type: research