Department of General Surgery, Xiangya Hospital Central South University, No. 87 Xiangya Road, Changsha, 410008, Hunan, People's Republic of China.
Department of General Surgery, Central South University Third Xiangya Hospital, No. 138 Tongzipo Road, Changsha, 410013, Hunan, People's Republic of China.
Sci Rep. 2021 Mar 15;11(1):5886. doi: 10.1038/s41598-021-85421-0.
Fibrotic tissue remodelling in nonalcoholic fatty liver disease (NAFLD) will probably emerge as the leading cause of end-stage liver disease in the coming decades, but the ability to diagnose liver fibrosis in NAFLD patients noninvasively is limited. The abnormal expression of tRNA-derived small RNA (tsRNA) in plasma provides a novel idea for noninvasive diagnosis of various diseases, however, the relationship between tsRNAs and NAFLD is still unknown. Here, we took advantage of small RNA-Seq technology to profile tsRNAs in NAFLD patients and found the ubiquitous presence of hepatic tsRNAs secreted into circulating blood. Verification in a cohort of 114 patients with NAFLD and 42 patients without NAFLD revealed that three tsRNAs (tRF-Val-CAC-005, tiRNA-His-GTG-001, and tRF-Ala-CGC-006) were significantly elevated in the plasma of NAFLD patients, and the expression level are associated with NAFLD activity score (calculated from 0 to 8) and fibrosis stage (scored from 0 to 4). In mouse models, we further found that increased plasma levels of these three tsRNAs were positively correlated with the degree of liver fibrosis. Our study potentially identifies a new class of NAFLD biomarkers and reveal the possible existence of tsRNAs in the blood that can be used to predict fibrogenesis risk in patients diagnosed with NAFLD.
非酒精性脂肪性肝病 (NAFLD) 的纤维组织重塑可能成为未来几十年终末期肝病的主要原因，但非侵入性诊断 NAFLD 患者肝纤维化的能力有限。血浆中 tRNA 衍生的小 RNA (tsRNA) 的异常表达为各种疾病的非侵入性诊断提供了一个新的思路，然而，tsRNAs 与 NAFLD 之间的关系尚不清楚。在这里，我们利用小 RNA-Seq 技术对 NAFLD 患者的 tsRNAs 进行了分析，发现肝脏 tsRNAs 普遍存在于分泌到循环血液中的情况。在 114 名 NAFLD 患者和 42 名非 NAFLD 患者的队列中进行验证，发现三种 tsRNAs（tRF-Val-CAC-005、tiRNA-His-GTG-001 和 tRF-Ala-CGC-006）在 NAFLD 患者的血浆中显著升高，其表达水平与 NAFLD 活动评分（从 0 到 8 计算）和纤维化阶段（从 0 到 4 评分）相关。在小鼠模型中，我们进一步发现这三种 tsRNAs 血浆水平的增加与肝纤维化程度呈正相关。我们的研究可能确定了一类新的 NAFLD 生物标志物，并揭示了血液中可能存在的可用于预测诊断为 NAFLD 的患者纤维化风险的 tsRNAs。
