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Remote ischemic preconditioning (RIPC) has been demonstrated to have protective effects against kidney injury caused by various factors; however, its role in LPS\u2010induced kidney injury remains unclear and its mechanisms require further exploration. Previous studies have shown that extracellular vesicles (EVs) induced by hypoxia mediated the renal protective effects of RIPC. In this study, we established a kidney injury model in rats by ligating the left ureter and injecting LPS into the renal pelvis, along with simultaneous removal of the right kidney (U\u2010L model); EVs were isolated from the plasma of rats subjected to RIPC or sham treatment and administered to U\u2010L model rats. Separately, EVs obtained from healthy human volunteers were applied to LPS\u2010treated human renal tubular epithelial cells (HK\u20102). Results indicated that RIPC\u2010EVs(R) reduced kidney injury caused by U\u2010L by inhibiting apoptosis, inflammation, and oxidative stress. In\u00a0vitro, RIPC\u2010EVs(H) alleviate LPS\u2010induced HK\u20102 cell injury by attenuating apoptosis and inflammation. Moreover, we identified 37 significantly upregulated differential proteins in the EVs sourced from human plasma after RIPC through 4D label\u2010free proteomics, including Tenascin\u2010C (TNC). Mechanistic studies revealed that RIPC\u2010EVs(H) activated \u03b2\u2010catenin, inhibited the p53 and NF\u2010\u03baB signaling pathways, and alleviated kidney injury. Clinical trial data showed that RIPC reduced the expression of kidney injury biomarkers in patients undergoing PCNL for kidney stones. Overall, the present study suggested that RIPC could mitigate kidney injury induced by LPS, possibly through the protective role of Tenascin\u2010C carried by EVs.<\/jats:p>","DOI":"10.1096\/fj.202600108rr","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T18:30:40Z","timestamp":1786732240000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Protective Effects and Mechanisms of Extracellular Vesicles in Remote Ischemic Preconditioning on Renal Injury Induced by Inflammation"],"prefix":"10.1096","volume":"40","author":[{"given":"Si","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Urology Zhongda Hospital, Southeast University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weipu","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Urology Zhongda Hospital, Southeast University  Nanjing 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