Ma Jianfeng, Gan Mailin, Chen Siyu, Shi Yuqian, Yang Yiting, Liu Chengming, Zhang Shunhua, Chen Lei, Zhu Kangping, Zhang Tinghuan, Luo Yi, Liu Yihui, Liu Bin, Niu Lili, Wang Yan, Zhu Li, Shen Linyuan
State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China.
Sichuan Dekon Livestock Foodstuff Group, Chengdu 610200, China.
Int J Biol Macromol. 2025 Mar;293:139167. doi: 10.1016/j.ijbiomac.2024.139167. Epub 2024 Dec 26.
Intrauterine growth retardation (IUGR) has become a difficult problem in animal husbandry and is often accompanied by the occurrence of metabolic syndrome. tRNA-derived small RNAs (tsRNAs) are a novel class of regulatory small noncoding RNAs. However, the involvement of tsRNA in regulating the mechanism of IUGR remains unclear. Here, we first characterized the tsRNA expression profiles in the liver of normal pigs and IUGR pigs through high-throughput sequencing. IUGR pigs exhibit significantly increased 17 tsRNA levels including tRF-Ile-GAT, tRF-Pro-TGG, tRF-Leu-CAA and tRF-Ala-TGC etc. Transcriptome sequencing further revealed 1244 upregulated and 762 downregulated differentially expressed genes in IUGR pig liver. Functional enrichment analysis found that DEGs were mainly involved in insulin resistance, metabolic pathways, etc. Metabolomics was performed to determine the metabolic changes between the normal and IUGR pigs. Then, We constructed a potential tsRNA regulatory network involved in metabolic pathways in IUGR pig liver. Moreover, combined metabolome and transcriptome analysis showed a disorder of glutathione metabolism in the IUGR pigs liver. We identified tRF-Ile-GAT as the potential target of interest. NCTC1469 liver cells were used to validate the preliminary function of tRF-Ile-GAT in vitro. Bioinformatics analyses and luciferase reporter assays further revealed that microsomal glutathione S-transferase 1 (MGST1) was the target gene of tRF-Ile-GAT. In addition, tRF-Ile-GAT overexpression inhibited antioxidant gene expression, glutathione and glutathione glutathione S-transferase levels in NCTC1469 cells, while an MGST1 overexpression reversed the above phenomenon. These findings provide new insights into the understanding of the molecular mechanisms of IUGR pathogenesis.
宫内生长受限（IUGR）已成为畜牧业中的一个难题，且常伴有代谢综合征的发生。tRNA衍生的小RNA（tsRNAs）是一类新型的调控性小非编码RNA。然而，tsRNA在调控IUGR机制中的作用仍不清楚。在此，我们首先通过高通量测序对正常猪和IUGR猪肝脏中的tsRNA表达谱进行了表征。IUGR猪表现出17种tsRNA水平显著升高，包括tRF-Ile-GAT、tRF-Pro-TGG、tRF-Leu-CAA和tRF-Ala-TGC等。转录组测序进一步揭示了IUGR猪肝中有1244个上调和762个下调的差异表达基因。功能富集分析发现，差异表达基因主要参与胰岛素抵抗、代谢途径等。进行代谢组学分析以确定正常猪和IUGR猪之间的代谢变化。然后，我们构建了一个IUGR猪肝中参与代谢途径的潜在tsRNA调控网络。此外，结合代谢组和转录组分析表明IUGR猪肝中谷胱甘肽代谢紊乱。我们将tRF-Ile-GAT鉴定为潜在的感兴趣靶点。使用NCTC1469肝细胞在体外验证tRF-Ile-GAT的初步功能。生物信息学分析和荧光素酶报告基因检测进一步揭示微粒体谷胱甘肽S-转移酶1（MGST1）是tRF-Ile-GAT的靶基因。此外，tRF-Ile-GAT过表达抑制了NCTC1469细胞中抗氧化基因的表达、谷胱甘肽和谷胱甘肽S-转移酶水平，而MGST1过表达则逆转了上述现象。这些发现为理解IUGR发病机制的分子机制提供了新的见解。
