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, a significant global healthcare burden, are mainly caused by the inhibition of cell proliferation and impaired angiogenesis. XB130 is an adaptor protein that regulates cell proliferation and migration. However, the role of XB130 in the development of diabetic skin ulcers remains unclear.
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 involved in diabetic skin ulcers. We investigated the effects of XB130 on wound healing using histological analyses. In addition, we used reverse transcription-quantitative polymerase chain reaction, Western blot, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining, immunofluorescence, wound healing, and tubule formation experiments 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 findings of this study indicated that 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.
Core Tip: The role of XB130 in the occurrence and development of diabetic skin ulcers healing is unclear. This study showed that the expression of XB130 was up-regulated in tissues of diabetic skin ulcers and human umbilical vein endothelial cells (HUVECs) stimulated by high glucose. Knockdown of XB130 promote the healing of skin wounds in mice, leading to an accelerated wound healing process and shortened wound healing time and alleviated hyperglycemia-induced cell proliferation inhibition and angiogenic impairment in HUVECs.