Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Sep 15, 2023; 14(9): 1369-1384
Published online Sep 15, 2023. doi: 10.4239/wjd.v14.i9.1369
XB130 inhibits healing of diabetic skin ulcers through the PI3K/Akt signalling pathway
Xin-Lin Zhu, Dong-Ying Hu, Zhao-Xiang Zeng, Wei-Wei Jiang, Tian-Yang Chen, Tian-Cheng Chen, Wan-Qing Liao, Wen-Zhi Lei, Wen-Jie Fang, Wei-Hua Pan
Xin-Lin Zhu, Dong-Ying Hu, Wei-Wei Jiang, Tian-Yang Chen, Tian-Cheng Chen, Wan-Qing Liao, Wen-Zhi Lei, Wen-Jie Fang, Wei-Hua Pan, Department of Dermatology, Shanghai Key Laboratory of Medical Mycology, Changzheng Hospital, Naval Medical University, Shanghai 200003, China
Zhao-Xiang Zeng, Department of Vascular Surgery, Department of Vascular Surgery, Changhai Hospital, Navy Medical University, Shanghai 20003, China
Author contributions: Pan WH, Liao WQ, Fang WJ, Lei WZ, and Zhu XL contributed to conceptualization; Zhu XL, Zeng ZX, and Jiang WW contributed to data curation; Zhu XL, Jiang WW, Zeng ZX, Hu DY, Chen TY, Chen TC, Liao WQ, Lei WZ, Fang WJ, and Pan WH contributed to investigation; Zhu XL, Zeng ZX, Jiang WW, Fang WJ, and Pan WH contributed to methodology; Pan WH contributed to project administration; Pan WH, Fang WJ, and Lei WZ contributed to supervision; Zeng ZX, Hu DY, and Zhu XL contributed to visualization; Zhu XL contributed to writing-original draft preparation; Liao WQ, Fang WJ, Pan WH, and Zhu XL contributed to writing-review and editing; Zhu XL, Hu DY, and Zeng ZX contribute equally to this paper.
Supported by the National Natural Science Foundation of China, No. 82272355; and Shanghai Science and Technology Committee, No. 21410750500.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Naval Medical University Medical Ethics Committee (Protocol No: 2020YffiPZ-102).
Conflict-of-interest statement: All the authors have declared no conflict of interest.
Data sharing statement: All data are provided in this study, and raw data can be requested to the corresponding author.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Wei-Hua Pan, PhD, Chief Doctor, Department of Dermatology, Shanghai Key Laboratory of Medical Mycology, Changzheng Hospital, Naval Medical University, No. 415 Fengyang Road, Shanghai 200003, China. panweihua9@sina.com
Received: May 24, 2023
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
Processing time: 112 Days and 10.9 Hours
ARTICLE HIGHLIGHTS
Research background

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.

Research motivation

To explore the role of XB130 in the development of diabetic skin ulcers.

Research objectives

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.

Research methods

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.

Research results

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.

Research conclusions

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.

Research perspectives

Decreasing the expression of XB130 could serve as a promising therapeutic approach to accelerate the healing of diabetic skin ulcers.