Oroxindin promotes angiogenesis in pressure ulcers through activating PI3K/AKT signaling pathway by PTEN suppression

Pressure ulcer (PU) is defined as localized tissue damage caused by prolonged pressure on any part of the body. Oroxindin (Oro) exhibits significant anti-inflammatory and anti-cancer effects. This study aimed to investigate the effect and underlying mechanism of Oro on PU. Angiogenesis was detected by CD31 immunohistochemistry and CD31/α-SMA immunofluorescence staining in vivo. Cell scratch assay, Transwell assay, and tube formation assay were performed to assess cell migration and angiogenesis in vitro. Phospho-kinase array was used to identify the pathway in Oro-treated human umbilical vein endothelial cells (HUVECs), and the mechanism was investigated by Western blot, luciferase reporter gene assay, biolayer interferometry assay, and molecular docking. Results showed that Oro accelerated wound healing and angiogenesis in the PU mouse model. Moreover, Oro promoted cell migration and tube formation in HUVECs. In addition, Oro activated the PI3K/Akt signaling pathway through the suppression of PTEN. PTEN overexpression reversed the effects of Oro on cell migration and tube formation in HUVECs. In conclusion, we demonstrated that Oro promoted PU wound healing in vivo and facilitated angiogenesis in HUVECs through activation of the PI3K/Akt signaling pathway via PTEN suppression, indicating the potential of Oro as an effective treatment for PU.

Angiogenesis; Oroxindin; PI3K/AKT; PTEN; Pressure ulcer.