{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T04:48:53Z","timestamp":1785041333040,"version":"3.55.0"},"reference-count":46,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T00:00:00Z","timestamp":1729123200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LY22H050004"],"award-info":[{"award-number":["LY22H050004"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LY23H050001"],"award-info":[{"award-number":["LY23H050001"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Renal interstitial fibrosis is a frequent pathological manifestation of lupus nephritis (LN). tRNA halves (tiRNAs) are acquired from tRNA\u2010derived small non\u2010coding RNAs (sncRNAs) and are associated with fibrosis. Our previous study indicated enhanced tiRNA\u2010Gly\u2010GCC\u2010002 (tiRNA002) levels in kidneys were positively related to LN\u2010related fibrosis. However, the precise molecular mechanism remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>The mimic and agomiR of tiRNA002 were introduced into tubular epithelial cells (TECs) and MRL\/lpr mice by transfection. The levels of gene and protein expressions were quantified using real\u2010time quantitative polymerase chain reaction (RT\u2010qPCR), Western blot and immunofluorescence assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>In TECs treated with LN serum, as well as in the kidneys of MRL\/lpr mice, high levels of tiRNA002 directly influenced the epithelial\u2010mesenchymal transition (EMT) and extracellular matrix (ECM) deposition. Furthermore, tiRNA002 overexpression promoted EMT in TECs and accelerated renal interstitial fibrosis in MRL\/lpr mice via Smad signalling. The target gene of tiRNA002, FKBP prolyl isomerase 5 (FKBP5), improved Smad signalling by interacting with phosphorylated Smad2\/3. Silencing FKBP5 alleviated LN serum\u2010 or tiRNA002\u2010mimic\u2010induced EMT in TECs. In addition, FKBP5 overexpression reversed the tiRNA002 knockdown\u2010mediated reduction of EMT and ECM accumulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>These findings indicated that tiRNA002 is markedly increased in LN, which facilitates renal fibrosis by promoting EMT via FKBP5\u2010mediated Smad signalling. Therefore, targeting tiRNA002 may be an innovative approach to treat renal interstitial fibrosis in LN.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.17364","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T01:24:48Z","timestamp":1729214688000},"page":"616-632","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["tiRNA\u2010Gly\u2010GCC\u2010002 promotes epithelial\u2010mesenchymal transition and fibrosis in lupus nephritis via FKBP5\u2010mediated activation of Smad"],"prefix":"10.1111","volume":"182","author":[{"given":"Xueting","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Nephrology The First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Institute of Chronic Nephropathy Wenzhou Medical University  Wenzhou 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