{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:00:44Z","timestamp":1790845244528,"version":"4.1.0"},"reference-count":0,"publisher":"Association of Basic Medical Sciences of FBIH","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomol Biomed"],"abstract":"<jats:p>Chronic kidney disease (CKD) is associated with progressive renal dysfunction, Klotho deficiency, and activation of profibrotic signaling. This study evaluated the functional and molecular effects of kidney-directed adeno-associated virus serotype 9 (AAV9)-mediated human Klotho delivery in experimental CKD. Forty-eight male mice were studied in six groups: sham, untreated 5\/6 nephrectomy, empty vector, low- and high-dose AAV9-Klotho, and recombinant Klotho. Vector was administered via the renal vein at week 4. The primary endpoint was week-16 serum creatinine, analyzed using a baseline-adjusted mixed model for repeated measures. High-dose AAV9-Klotho was associated with lower serum creatinine than empty vector (adjusted difference, \u221220.6 \u00b5mol\/L; 95% confidence interval, \u221233.3 to \u22127.9; p\u00a0= 0.0018), with concordant changes in blood urea nitrogen, proteinuria, and urinary albumin-to-creatinine ratio. Human Klotho expression increased with vector dose, accompanied by recovery of endogenous mouse Klotho. Fibrosis-associated and inflammatory markers, transforming growth factor-\u03b2 receptor I abundance, and phosphorylation of mothers against decapentaplegic homologs 2 and 3 (Smad2\/3) were lower after treatment, whereas transforming growth factor-\u03b21 (TGF-\u03b21) abundance remained unchanged. These findings associate kidney-directed AAV9-Klotho delivery with improved renal-function measures and modulation of TGF-\u03b21\/Smad2\/3 signaling in experimental CKD. Histological antifibrotic efficacy and direct receptor-level mechanisms remain unconfirmed.<\/jats:p>","DOI":"10.17305\/bb.2026.14798","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:37:48Z","timestamp":1790843868000},"source":"Crossref","is-referenced-by-count":0,"title":["Kidney-directed AAV9 Klotho gene delivery improves renal function in a mouse model of chronic kidney disease"],"prefix":"10.17305","author":[{"given":"Chaoying","family":"Yan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Jian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"6922","published-online":{"date-parts":[[2026,10,1]]},"container-title":["Biomolecules and Biomedicine"],"original-title":[],"link":[{"URL":"https:\/\/bjbms.org\/ojs\/index.php\/bjbms\/article\/download\/14798\/4346","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bjbms.org\/ojs\/index.php\/bjbms\/article\/download\/14798\/4346","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:37:48Z","timestamp":1790843868000},"score":1,"resource":{"primary":{"URL":"https:\/\/bjbms.org\/ojs\/index.php\/bjbms\/article\/view\/14798"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,1]]},"references-count":0,"URL":"https:\/\/doi.org\/10.17305\/bb.2026.14798","relation":{},"ISSN":["2831-090X","2831-0896"],"issn-type":[{"value":"2831-090X","type":"electronic"},{"value":"2831-0896","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10,1]]}}}