Proteomic analysis of foot ulcer tissue reveals novel potential therapeutic targets of wound healing in diabetic foot ulcers

Yanling Wang; Yinzhen Pi; Li Hu; Zhihong Peng; Hanyang Hu; Jinjin Zhao; Yun Zhou; Dongbo Wang

doi:10.1016/j.compbiomed.2023.106858

Proteomic analysis of foot ulcer tissue reveals novel potential therapeutic targets of wound healing in diabetic foot ulcers

Comput Biol Med. 2023 Jun:159:106858. doi: 10.1016/j.compbiomed.2023.106858. Epub 2023 Apr 13.

Authors

Yanling Wang¹, Yinzhen Pi², Li Hu², Zhihong Peng³, Hanyang Hu⁴, Jinjin Zhao², Yun Zhou², Dongbo Wang⁵

Affiliations

¹ The First Hospital of Changsha, Changsha, 410005, China; The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University, Changsha, 410008, China; Changsha Maternal and Child Health Hospital Affiliated to Hunan Normal University, Changsha, 410007, China.
² The First Hospital of Changsha, Changsha, 410005, China; The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University, Changsha, 410008, China.
³ National & Local Joint Engineering Research Center of High-Throughput Drug Screening Technology, College of Health Science and Engineering, Hubei University, Wuhan, China.
⁴ Department of Histology and Embryology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China.
⁵ The First Hospital of Changsha, Changsha, 410005, China; The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University, Changsha, 410008, China. Electronic address: 1391620610@qq.com.

PMID: 37087778
DOI: 10.1016/j.compbiomed.2023.106858

Abstract

Foot ulcers are a common complication of diabetes mellitus, which is associated with high morbidity and mortality among diabetic patients. The present study aims to investigate novel wound healing pathways in diabetic foot ulcers (DFU) through proteomics and a network pharmacology analysis. Tandem mass tag (TMT) labeled quantitative proteomics method was performed to evaluate the protein expression profile in wound tissues from healthy controls (HC) and DFU. Kyoto Encyclopedia of Genes (KEGG) and Genomes enrichment analysis (GO) was conducted based on differentially expressed proteins (DEPs) to discover the potential pathways associated with DFU. Western blot analysis was used to confirm the probable DFU-related targets. Proteomics analysis discovered 509 DEPs (248 upregulated and 261 downregulated proteins). Go and KEGG further evaluated the DEPs to discover the DFU-related pathways. According to network pharmacology study, three main targets (metalloproteinase 9 (MMP9), Fatty acid-binding protein 5 (FABP5), and integrin subunit alpha M (ITGAM)) play crucial roles in signaling pathways. Staphylococcus aureus infection and leukocyte transendothelial migration pathways significantly enriched in DFU. In addition, it was confirmed that three critical targets were elevated in diabetes mouse wound tissues. The study confirmed the presence of protein alterations in the wound-healing process of DFU mice and may provide fresh insights into the molecular mechanisms driving DFU.

Keywords: Diabetic foot ulcers (DFU); Fatty acid-binding protein 5 (FABP5); Integrin subunit alpha M (ITGAM); Metalloproteinase 9 (MMP9); TMT labeled Quantitative proteomics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Diabetes Mellitus*
Diabetic Foot* / genetics
Mice
Proteomics
Wound Healing