5′tiRNA-His-GTG促进Smad3磷酸化加重心脏纤维化*

doi:10.3870/j.issn.1672-0741.25.10.030

华中科技大学学报（医学版） ›› 2026, Vol. 55 ›› Issue (1): 1-10.doi: 10.3870/j.issn.1672-0741.25.10.030

• 论著 • 下一篇

5′tiRNA-His-GTG促进Smad3磷酸化加重心脏纤维化^*

蔡子阳, 蔡煜炜, 严江涛^△

华中科技大学同济医学院附属同济医院心血管内科, 武汉 430030

收稿日期:2025-10-23 出版日期:2026-02-15 发布日期:2026-02-10
通讯作者: ^△E-mail:jtyan@tjh.tjmu.edu.cn
作者简介:蔡子阳,男,2001年生,医学硕士,E-mail:sakespicy@163.com
基金资助:
^*国家自然科学基金资助项目(No.82170392)

5′tiRNA-His-GTG Aggravates Cardiac Fibrosis through Promoting Smad3 Phosphorylation

Cai Ziyang, Cai Yuwei, Yan Jiangtao^△

Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

Received:2025-10-23 Online:2026-02-15 Published:2026-02-10
Contact: ^△E-mail:jtyan@tjh.tjmu.edu.cn

摘要/Abstract

摘要： 目的本研究旨在探索心脏纤维化相关的转运RNA衍生小RNA(tsRNA),并探究其调控机制与临床相关性。方法通过PANDORA-seq筛选心脏纤维化相关tsRNA,发现5′tiRNA-His-GTG表达显著上调。采用qRT-PCR、Western blot、CCK-8、EdU等方法评估5′tiRNA-His-GTG对心脏纤维化过程的影响。此外,通过RNA pulldown和RIP-qPCR探究5′tiRNA-His-GTG在TGF-β1/Smad3通路中的调控机制。检测临床病患血浆样本中5′tiRNA-His-GTG的表达水平,并使用多因素Logistic回归分析5′tiRNA-His-GTG是否构成冠状动脉粥样硬化性心脏病(CAD)的独立危险因素。结果过表达5′tiRNA-His-GTG促进心脏成纤维细胞的纤维化反应,增强TGF-β1/Smad3通路中Smad3的磷酸化进而激活下游纤维化相关基因COL1A1和ACTA2的转录和翻译。5′tiRNA-His-GTG与Smad3互相作用。5′tiRNA-His-GTG在CAD组血浆中的水平大约为对照组的4倍,并且5′tiRNA-His-GTG与CAD发病之间存在独立相关性。结论 5′tiRNA-His-GTG通过与Smad3相互作用促进Smad3磷酸化,进而调节心脏纤维化过程。

关键词: 心脏纤维化, 转运RNA衍生小RNA, 非编码小RNA, 磷酸化, TGF-β1/Smad3通路

Abstract: Objective This study aimed to explore tRNA-derived small RNAs(tsRNAs)associated with cardiac fibrosis and to investigate their regulatory mechanisms and clinical relevance. Methods We conducted a screening to identify tsRNAs relevant to cardiac fibrosis via PANDORA-seq and identified a significant increase in the expression of 5′tiRNA-His-GTG.We used qRT-PCR,Western blotting,CCK-8,and EdU to assess the effects of 5′tiRNA-His-GTG on the progression of cardiac fibrosis.Additionally,we utilized RNA pulldown and RIP-qPCR to explore the regulatory mechanism of 5′tiRNA-His-GTG in the TGF-β1/Smad3 pathway.We measured the expression level of 5′tiRNA-His-GTG in plasma samples from clinical patients and applied multivariate logistic regression analysis to determine whether 5′tiRNA-His-GTG is an independent risk factor for coronary atherosclerotic heart disease(CAD). Results Overexpression of 5′tiRNA-His-GTG promoted the fibrotic response in cardiac fibroblasts,increased the phosphorylation of Smad3 in the TGF-β1/Smad3 pathway,and activated the transcription and translation of downstream fibrosis-related genes,including COL1A1 and ACTA2.Mechanistically,5′tiRNA-His-GTG interacted with Smad3.The plasma levels of 5′tiRNA-His-GTG in the CAD group were approximately four fold higher than those in the control group,and 5′tiRNA-His-GTG was independently correlated with CAD onset. Conclusion Our results demonstrate that 5′tiRNA-His-GTG promotes Smad3 phosphorylation by interacting with Smad3,thus modulating the progression of cardiac fibrosis.

Key words: cardiac fibrosis, tsRNA, sncRNA, phosphorylation, TGF-β1/Smad3 pathway

中图分类号:

R541.4

蔡子阳, 蔡煜炜, 严江涛. 5′tiRNA-His-GTG促进Smad3磷酸化加重心脏纤维化^*[J]. 华中科技大学学报（医学版）, 2026, 55(1): 1-10.

Cai Ziyang, Cai Yuwei, Yan Jiangtao. 5′tiRNA-His-GTG Aggravates Cardiac Fibrosis through Promoting Smad3 Phosphorylation[J]. Acta Medicinae Universitatis Scientiae et Technologiae Huazhong, 2026, 55(1): 1-10.

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5′tiRNA-His-GTG促进Smad3磷酸化加重心脏纤维化^*

5′tiRNA-His-GTG Aggravates Cardiac Fibrosis through Promoting Smad3 Phosphorylation

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