Molecular mechanism underlying the protective effects of ischemic preconditioning in total knee arthroplasty.
10.1016/j.cjtee.2024.02.007
- Author:
Yongli WANG
1
;
Bencai DU
2
;
Xueliang HAN
2
;
Lianjun QU
3
,
4
Author Information
1. Department of Anesthesiology, the 80th Group Military Hospital of the Chinese People's Liberation Army, Weifang, 261000, Shandong province, China.
2. Orthopedic Center, Sunshine Union Hospital, Weifang, 261000, Shandong province, China.
3. Orthopedic Center, Sunshine Union Hospital, Weifang, 261000, Shandong province, China. Electronic address: LianjunQu@
4. com.
- Publication Type:Journal Article
- Keywords:
Differentially expressed gene;
Function and pathway enrichment analysis;
Ischemic preconditioning;
Total knee arthroplasty;
ceRNA network
- MeSH:
Humans;
Arthroplasty, Replacement, Knee;
Ischemic Preconditioning;
RNA, Long Noncoding/genetics*;
Protein Interaction Maps;
MicroRNAs/genetics*;
RNA, Messenger/genetics*;
Gene Regulatory Networks
- From:
Chinese Journal of Traumatology
2025;28(4):257-268
- CountryChina
- Language:English
-
Abstract:
PROPOSE:To investigate the molecular mechanisms underlying the protective effects of ischemic preconditioning (IPC) in patients undergoing total knee arthroplasty.
METHODS:GSE21164 was extracted from an online database, followed by an investigation of differentially expressed genes (DEGs) between IPC treatment samples at 2 time points (T0T and T1T). Function and pathway enrichment analyses were performed on the DEGs. A protein-protein interaction network was constructed to identify hub genes according to 5 different algorithms, followed by enrichment analysis. In addition, long noncoding RNAs (lncRNAs) were identified between the T0T and T1T samples. Furthermore, a competing endogenous RNA network was predicted based on the identified lncRNA-messenger RNA (mRNA), lncRNA-microRNA (miRNA), and mRNA-miRNA relationships revealed in this study. Finally, a drug-gene network was investigated. Statistical analyses were performed using GraphPad Prism 8.0. Differences between groups were determined using an unpaired t-test. p < 0.05 was considered significant.
RESULTS:A total of 343 DEGs at T0 and 10 DEGs at T1 were identified and compared with their respective control groups, followed by 100 DEGs between T0T and T1T. Based on these 100 DEGs, protein-protein interaction network analysis revealed 9 hub genes, mainly with mitochondria-related functions and the carbon metabolism pathway. Six differentially expressed lncRNAs were investigated between T0T and T1T. A competing endogenous RNA network was constructed using 259 lncRNA-miRNA-mRNA interactions, including alpha-2-macroglobulin antisense RNA 1-miR-7161-5p-iron-sulfur cluster scaffold. Finally, 13 chemical drugs associated with the hub genes were explored.
CONCLUSION:Iron-sulfur cluster scaffold may promote IPC-induced ischemic tolerance mediated by alpha-2-macroglobulin antisense RNA 1-miR-7161-5p axis. Moreover, IPC may induce a protective response after total knee arthroplasty via mitochondria-related functions and the carbon metabolism pathway, which should be further validated in the near future.
