Academic Journal
Genome-wide KAS-Seq mapping of leukocytes in ischemia-reperfusion model reveals IL7R as a potential therapeutic target for ischemia-reperfusion injury
| Title: | Genome-wide KAS-Seq mapping of leukocytes in ischemia-reperfusion model reveals IL7R as a potential therapeutic target for ischemia-reperfusion injury |
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| Authors: | Lei Zhang, Maimaitiyasen Duolikun, Hangyu Chen, Zihao Wang, Xuehui Li, Hong Xiao, Yuchao Dong, Haoyu Chen, Fengyong Liu, Shiyong Fan, Jian Lin, Long Chen |
| Source: | Scientific Reports, Vol 15, Iss 1, Pp 1-15 (2025) |
| Publisher Information: | Nature Portfolio, 2025. |
| Publication Year: | 2025 |
| Collection: | LCC:Medicine LCC:Science |
| Subject Terms: | KAS-Seq, Ischemia–reperfusion injury, Leukocytes, IL7R, Target, Medicine, Science |
| More Details: | Abstract Ischemia–reperfusion injury (IRI) is one of the leading causes of mortality and disability worldwide. Owing to its complex pathogenesis, there is still a lack of effective therapeutic targets in clinical practice, and exploring the mechanism and targets of IRI is still a major clinical challenge. This study aimed to explore the genetic alterations in leukocytes in peripheral blood after ischemia–reperfusion, aiming to discover new biomarkers and potential therapeutic targets. KAS-Seq (Kethoxal-assisted single-strand DNA sequencing) was used to obtain gene expression profiles of circulating leukocytes in a porcine ischemia–reperfusion model at 24, 48, and 72 h post-ischemia‒reperfusion. This method integrated genes that exhibited regular changes over time. In this study, we thoroughly analyzed the dynamic changes in gene expression post-IRI, revealing significant enrichment in key signaling pathways that regulate immune responses and T-cell activation over time. Our identification of the interleukin-7 receptor (IL7R) was particularly striking, as it plays a crucial molecular role in IRI. Additionally, using database mining technology, we confirmed the close relationship between IL7R and IRI, explored the interaction between interferon-γ (IFNG) and IL7R in T-cell activation, and clarified their joint influence on ischemia–reperfusion injury. Using KAS-Seq analysis of leukocytes from peripheral blood, we successfully delineated the temporal patterns of gene expression and changes in signal transduction pathways in porcine models of ischemia–reperfusion. Subsequent in-depth analysis identified IL7R as a potential novel therapeutic target for IRI. The pivotal role of this gene in modulating immune responses provides innovative avenues for the development of IRI treatments. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2045-2322 |
| Relation: | https://doaj.org/toc/2045-2322 |
| DOI: | 10.1038/s41598-025-90457-7 |
| Access URL: | https://doaj.org/article/f6161c312bff438e99518b09e4583372 |
| Accession Number: | edsdoj.f6161c312bff438e99518b09e4583372 |
| Database: | Directory of Open Access Journals |
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| ISSN: | 20452322 |
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| DOI: | 10.1038/s41598-025-90457-7 |
| Published in: | Scientific Reports |
| Language: | English |