Published online Sep 15, 2023. doi: 10.4239/wjd.v14.i9.1369
Peer-review started: May 24, 2023
First decision: June 12, 2023
Revised: July 6, 2023
Accepted: August 2, 2023
Article in press: August 2, 2023
Published online: September 15, 2023
Diabetic skin ulcers are mainly caused by the inhibition of cell proliferation and impaired angiogenesis, a high percentage (15%-27%) of diabetic foot skin ulcer cases require lower extremity amputation owing to treatment failure. XB130 is an adaptor protein that regulates cell proliferation and migration.
To explore the role of XB130 in the development of diabetic skin ulcers.
To investigate whether XB130 can regulate the inhibition of proliferation and vascular damage induced by high glucose. Additionally, we aim to determine whether XB130 is involved in the healing process of diabetic skin ulcers, along with its molecular mechanisms.
We conducted RNA-sequencing analysis to identify the key genes. The RT-qPCR, Western blot, TUNEL staining, immunofluorescence, wound healing, and tubule formation experiments were used to investigate their effects on cellular processes in human umbilical vein endothelial cells (HUVECs) stimulated with high glucose. Finally, we performed functional analysis to elucidate the molecular mechanisms underlying diabetic skin ulcers.
RNA-sequencing analysis showed that the expression of XB130 was up-regulated in the tissues of diabetic skin ulcers. Knockdown of XB130 promoted the healing of skin wounds in mice, leading to an accelerated wound healing process and shortened wound healing time. At the cellular level, knockdown of XB130 alleviated high glucose-induced inhibition of cell proliferation and angiogenic impairment in HUVECs. Inhibition of the PI3K/Akt pathway removed the proliferative effects and endothelial protection mediated by XB130.
The expression of XB130 is up-regulated in high glucose-stimulated diabetic skin ulcers and HUVECs. Knockdown of XB130 promotes cell proliferation and angiogenesis via the PI3K/Akt signalling pathway, which accelerates the healing of diabetic skin ulcers.
Decreasing the expression of XB130 could serve as a promising therapeutic approach to accelerate the healing of diabetic skin ulcers.