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

doi:10.3870/j.issn.1672-0741.25.10.030

Abstract

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

CLC Number:

R541.4

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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