tRF-1-ArgTCG-1-1 promotes renal fibrosis by regulating β-catenin

Area of Science:

• Molecular Biology
• Renal Pathophysiology
• Noncoding RNA Research

Background:

• Renal fibrosis (RF) is a key driver of chronic kidney disease (CKD) progression.
• Noncoding RNAs (ncRNAs), including tRNA-derived fragments (tRFs), are increasingly recognized for their roles in CKD.
• The specific function of tRFs in RF remains largely unexplored.

Purpose of the Study:

• To investigate the role of tRFs in renal fibrosis.
• To identify specific dysregulated tRFs in patients with RF.
• To elucidate the molecular mechanism of identified tRFs in RF pathogenesis.

Main Methods:

• Human small RNA microarray analysis of urine-derived renal tubular epithelial cells from RF patients.
• RT-PCR validation in clinical urine samples.
• Investigated tRF-1-ArgTCG-1-1 interaction with β-catenin using Hypro-MS and PRM, and functional roles via ASO-mediated knockdown in TGF-β1-treated HK-2 cells.

Main Results:

• Microarray identified tRF-1-ArgTCG-1-1 as upregulated in RF.
• RT-PCR confirmed elevated tRF-1-ArgTCG-1-1 in CKD patients' urine, correlating with impaired renal function.
• tRF-1-ArgTCG-1-1 interacts with β-catenin, and its silencing reduces β-catenin and RF markers in vitro.

Conclusions:

• Renal tubular epithelial cell tRF-1-ArgTCG-1-1 plays a significant role in RF.
• The tRF-1-ArgTCG-1-1/β-catenin pathway presents a potential therapeutic target for CKD and RF.