Zheng Lucheng, Yang Xue, Fan Qingcan, Liu Ben, Hu Wei, Cui Yan
College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China.
College of Life Science and Resources and Environment, Yichun University, Yichun, China.
Front Vet Sci. 2023 May 3;10:1149333. doi: 10.3389/fvets.2023.1149333. eCollection 2023.
Wound healing is very important for the maintenance of immune barrier integrity, which has attracted wide attention in past 10 years. However, no studies on the regulation of cuproptosis in wound healing have been reported.
In this study, the skin injury model was constructed in Gnxi goats, and the function, regulatory network and hub genes of the skin before and after the injury were comprehensively analyzed by transcriptomics.
The results showed that there were 1,438 differentially expressed genes (DEGs), genes up-regulated by 545 and genes down-regulated by 893, which were detected by comparing day 0 and day 5 posttraumatic skin. Based on GO-KEGG analysis, DEGs that were up-regulated tended to be enriched in lysosome, phagosome, and leukocyte transendothelial migration pathways, while down-regulated DEGs were significantly enriched in adrenergic signaling in cardiomyocytes and calcium signaling pathway. There were 166 overlapped genes (DE-CUGs) between DEGs and cuproptosis-related genes, with 72 up-regulated DE-CUGs and 94 down-regulated DE-CUGs. GOKEGG analysis showed that up-regulated DE-CUGs were significantly enriched in ferroptosis, leukocyte transendothelial migration and lysosome pathways, while down-regulated DE-CUGs were significantly enriched in Apelin signaling pathway and tyrosine metabolism pathways. By constructing and analyzing of protein-protein interaction (PPI) networks of DEGs and DE-CUGs, 10 hub DEGs (ENSCHIG00000020079, PLK1, AURKA, ASPM, CENPE, KIF20A, CCNB2, KIF2C, PRC1 and KIF4A) and 10 hub DE-CUGs (MMP2, TIMP1, MMP9, MMP14, TIMP3, MMP1, EDN1, GCAT, SARDH, and DCT) were obtained, respectively.
This study revealed the hub genes and important wound healing pathways in Ganxi goats, and identified the correlation between wound healing and cuproptosis for the first time, and found that MMP2, TIMP1, MMP9, and EDN1 were the core genes associated. This study enriched the transcriptome data of wound healing in Ganxi goats and expanded the research direction of cuproptosis.
伤口愈合对于维持免疫屏障完整性非常重要，在过去十年中受到了广泛关注。然而，尚未有关于伤口愈合中铜死亡调节的研究报道。
在本研究中，构建了湘西山羊皮肤损伤模型，并通过转录组学全面分析了损伤前后皮肤的功能、调控网络和枢纽基因。
结果显示，通过比较创伤后第0天和第5天的皮肤，共检测到1438个差异表达基因（DEG），其中上调基因545个，下调基因893个。基于GO-KEGG分析，上调的DEG倾向于富集在溶酶体、吞噬体和白细胞跨内皮迁移途径中，而下调的DEG则显著富集在心肌细胞中的肾上腺素能信号通路和钙信号通路中。DEG与铜死亡相关基因之间有166个重叠基因（DE-CUG），其中上调的DE-CUG有72个，下调的DE-CUG有94个。GO-KEGG分析表明，上调的DE-CUG显著富集在铁死亡、白细胞跨内皮迁移和溶酶体途径中，而下调的DE-CUG则显著富集在Apelin信号通路和酪氨酸代谢途径中。通过构建和分析DEG和DE-CUG的蛋白质-蛋白质相互作用（PPI）网络，分别获得了10个枢纽DEG（ENSCHIG00000020079、PLK1、AURKA、ASPM、CENPE、KIF20A、CCNB2、KIF2C、PRC1和KIF4A）和10个枢纽DE-CUG（MMP2、TIMP1、MMP9、MMP14、TIMP3、MMP1、EDN1、GCAT、SARDH和DCT）。
本研究揭示了湘西山羊的枢纽基因和重要的伤口愈合途径，并首次确定了伤口愈合与铜死亡之间的相关性，发现MMP2、TIMP1、MMP9和EDN1是相关的核心基因。本研究丰富了湘西山羊伤口愈合的转录组数据，拓展了铜死亡的研究方向。
