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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\u20111:30\u2011Gln\u2011CTG\u20114, was markedly decreased in proximal renal tubules and highly correlated with TIF in DKD mice. The overexpression of tRF\u20111:30\u2011Gln\u2011CTG\u20114 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\u20111:30\u2011Gln\u2011CTG\u20114. 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\u20111:30\u2011Gln\u2011CTG\u20114 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.<\/jats:p>","DOI":"10.1038\/s41419-026-09112-2","type":"journal-article","created":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T14:13:07Z","timestamp":1784383987000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tubular tRF\u20111:30\u2011Gln\u2011CTG\u20114 attenuates tubulointerstitial fibrosis by mitigating FBXO7-mediated mitophagy defect in diabetic kidney disease"],"prefix":"10.1038","volume":"17","author":[{"given":"Jia-ling","family":"Ji","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-yang","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-yue","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Huo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-min","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gao-ting","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan-wen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuo-lin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5359-8657","authenticated-orcid":false,"given":"Ai-qing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,18]]},"reference":[{"key":"9112_CR1","doi-asserted-by":"publisher","first-page":"e13612","DOI":"10.1111\/1753-0407.13612","volume":"16","author":"Z Bloomgarden","year":"2024","unstructured":"Bloomgarden Z. 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