Authors
Jia-Ling Ji, Yun-Yang Qiao, Jia-Yue Sun, Ying Huo, Hui-Min Shi, Gao-Ting Qu, Shan-Wen Li, Chan Huang, Yu Feng, Pei Zhang, Ling Ding, Zuo-Lin Li, Ai-Qing Zhang
Published in
Cell death & disease. Jul 18, 2026. Epub Jul 18, 2026.
Abstract
Tubulointerstitial fibrosis (TIF) is a crucial pathological feature and inevitable consequence of progressive diabetic kidney disease (DKD). Transfer RNA-derived fragments (tRFs), a novel class of small non-coding RNA by cleavage of tRNAs, have recently attracted attention due to their functional significance in diverse biological processes. However, the role of tRFs in TIF is largely elusive. In the present study, we found that a tRF, tRF‑1:30‑Gln‑CTG‑4, was markedly decreased in proximal renal tubules and highly correlated with TIF in DKD mice. The overexpression of tRF‑1:30‑Gln‑CTG‑4 revealed a therapeutic effect against TIF. Further, RNA pull-down and RNA-immunoprecipitation assay were performed to identify that FBXO7, an adaptor protein in the SCF E3 ligase complex, was the targeted protein of tRF‑1:30‑Gln‑CTG‑4. Mass spectrometry and co-immunoprecipitation experiments revealed that PINK1, a master mitophagy-regulating protein, acted as the substrate of FBXO7 in tubular epithelial cells. Mechanistically, elevated FBXO7 promoted mitophagy defect through mediating PINK1 ubiquitylation and proteasomal degradation. The overexpression of tRF‑1:30‑Gln‑CTG‑4 alleviated defective mitophagy. Taken together, this study not only represents a novel insight into the pathogenesis of TIF but also provides a promising therapeutic targeting for the delaying the progression of DKD.
PMID:
42471341
Bibliographic data and abstract were imported from PubMed on 19 Jul 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 3
- Comments 0