tRF-1-ArgTCG1-1通过调节β-catenin促进肾纤维化
tRF-1-ArgTCG-1-1 promotes renal fibrosis by regulating β-catenin.
摘要(中文译文)
肾纤维化（RF）是慢性肾脏病（CKD）进展至终末期肾衰竭的关键病理因素。近年来，非编码RNA（ncRNA）在CKD中的作用受到关注。tRNA衍生片段（tRF）是一类来源于tRNA的小非编码RNA。迄今为止，tRF在肾纤维化中的功能尚未被探索。本研究采用人类小RNA微阵列分析，鉴定肾纤维化患者尿源性肾小管上皮细胞中失调的tRF。采用RT-PCR在临床样本中进行验证。采用羟胺介导的蛋白沉淀质谱法（Hypro-MS）、平行反应监测（PRM）以及反义寡核苷酸（ASO）介导的敲低技术，研究tRF-1-ArgTCG-1-1与β-catenin之间的相互作用及其在TGF-β1处理的HK-2细胞中的功能作用。微阵列分析鉴定出tRF-1-ArgTCG-1-1是肾纤维化患者尿源性肾小管上皮细胞中表达上调的tRF。RT-PCR进一步证实，tRF-1-ArgTCG-1-1在CKD患者尿液样本中的表达显著升高，并与肾功能受损及较高的肾纤维化风险相关。Hypro-MS和PRM分析表明tRF-1-ArgTCG-1-1与β-catenin之间存在相互作用。ASO介导的tRF-1-ArgTCG-1-1沉默降低了HK-2细胞中β-catenin的表达。此外，单独沉默tRF-1-ArgTCG-1-1或同时沉默tRF-1-ArgTCG-1-1与β-catenin，均可减弱TGF-β1诱导的肾纤维化相关标志物的表达。总体而言，这些发现表明肾小管上皮细胞中的tRF-1-ArgTCG-1-1在肾纤维化中发挥关键作用，且tRF-1-ArgTCG-1-1/β-catenin通路是CKD和肾纤维化的潜在治疗靶点。
Abstract
Renal fibrosis (RF) is a crucial pathological factor in the progression of chronic kidney disease (CKD) to end-stage renal failure. The role of noncoding RNAs (ncRNAs) in CKD has been researched recently. tRNA-derived fragments (tRFs) constitute a class of small ncRNAs originating from tRNAs. To date, the function of tRFs in RF remains unexplored. Human small RNA microarray analysis was performed to identify dysregulated tRFs in urine-derived renal tubular epithelial cells from patients with RF. RT-PCR was used for validation in clinical samples. Hydroxylamine-mediated protein precipitation mass spectrometry (Hypro-MS), parallel reaction monitoring (PRM), and antisense oligonucleotide (ASO)-mediated knockdown were used to investigate the interaction between tRF-1-ArgTCG-1-1 and β-catenin and its functional role in TGF-β1-treated HK-2 cells. Microarray profiling identified tRF-1-ArgTCG-1-1 as an upregulated tRF in urine-derived renal tubular epithelial cells from patients with RF. RT-PCR further confirmed that tRF-1-ArgTCG-1-1 expression was significantly increased in urine samples from patients with CKD and was associated with impaired renal function and a higher risk of RF. Hypro-MS and PRM analyses demonstrated an interaction between tRF-1-ArgTCG-1-1 and β-catenin. ASO-mediated silencing of tRF-1-ArgTCG-1-1 reduced β-catenin expression in HK-2 cells. Moreover, silencing of tRF-1-ArgTCG-1-1, alone or together with β-catenin, attenuated TGF-β1-induced expression of RF-related markers . Overall, these findings suggest that renal tubular epithelial cells tRF-1-ArgTCG-1-1 play a key role in RF and that the tRF-1-ArgTCG-1-1/β-catenin pathway is a potential therapeutic target for CKD and RF.
如何引用
AMA
Ling Jin, Ci Wang, Yuye Yan, Yuye Chen, Zihao Xiao, Yajie Wang, et al. tRF-1-ArgTCG-1-1 promotes renal fibrosis by regulating β-catenin.. Renal failure. 2026; doi:10.1080/0886022X.2026.2670055.
APA
Ling Jin, Ci Wang, Yuye Yan, Yuye Chen, Zihao Xiao, Yajie Wang, et al (2026). tRF-1-ArgTCG-1-1 promotes renal fibrosis by regulating β-catenin.. Renal failure. https://doi.org/10.1080/0886022X.2026.2670055
GB/T 7714
Ling Jin, Ci Wang, Yuye Yan, Yuye Chen, Zihao Xiao, Yajie Wang, et al. tRF-1-ArgTCG-1-1 promotes renal fibrosis by regulating β-catenin.[J]. Renal failure, 2026 doi:10.1080/0886022X.2026.2670055.
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