{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T01:30:21Z","timestamp":1790040621930,"version":"4.0.1"},"reference-count":49,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,11,23]],"date-time":"2025-11-23T00:00:00Z","timestamp":1763856000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,23]],"date-time":"2025-11-23T00:00:00Z","timestamp":1763856000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Bladder fibrosis represents a widespread global health challenge associated with substantial socioeconomic burden. To date, no effective therapeutic interventions are available to halt or reverse its progression. Small activating RNA (saRNA)\u2010based therapy has recently garnered increasing interest due to its high target specificity and potent efficacy. Nevertheless, the clinical translation of saRNA is hampered by inherent limitations including structural instability, nuclease sensitivity, and inefficient cellular internalization. In this study, single\u2010cell and bulk transcriptomic analyses are integrated, which reveal that SIRT1 is the only sirtuin family member significantly downregulated in both fibrotic bladder tissues and activated fibroblasts. To address this, a tetrahedral DNA functionalized with saRNA targeting SIRT1 activation is engineered, termed TSA. TSA exhibits exceptional biocompatibility and markedly attenuates bladder dysfunction and fibrotic remodeling in a bladder outlet obstruction model. Mechanistically, TSA administration robustly restores SIRT1 expression,\u00a0facilitating FOXO3A deacetylation and alleviating its transcriptional repression of BNIP3. This cascade leads to the activation of PINK1\u2010PARKIN\u2010mediated mitophagy, suppresses mitochondrial reactive oxygen species accumulation, and ultimately leads to the inhibition of fibroblast activation and collagen deposition. These compelling findings underscore the therapeutic potential of TSA as a promising strategy for the treatment of bladder fibrosis, with broad implications for clinical application.<\/jats:p>","DOI":"10.1002\/advs.202519527","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T05:19:39Z","timestamp":1763961579000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Sirtuin\u20101\u2010Targeted Gene\u2010Activating Tetrahedral DNA Attenuates Bladder Fibrosis by Restoring Mitophagy in Fibroblasts via the SIRT1\u2010FOXO3\u2010BNIP3 Axis"],"prefix":"10.1002","volume":"13","author":[{"given":"Wei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Urology Institute of Urology (Laboratory of Reconstructive Urology) West China Hospital Sichuan University Chengdu Sichuan 610041 P. R. 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