{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T10:27:44Z","timestamp":1781519264471,"version":"3.54.1"},"reference-count":65,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T00:00:00Z","timestamp":1692576000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Exercise training exerts protective effects against sepsis\u2010associated multiple organ dysfunction. This study aimed to investigate whether aerobic exercise protected against sepsis\u2010associated acute kidney injury (AKI) via modulating R\u2010spondin 3 (RSPO3) expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To investigate the effects of aerobic exercise on lipopolysaccharide (LPS)\u2010induced AKI, LPS (20\u2009mg\/kg) was intraperitoneally injected after six weeks of treadmill training. To investigate the role of RSPO3 in LPS\u2010induced AKI, wild\u2010type (WT) or inducible endothelial cell\u2010specific RSPO3 knockout (RSPO3<jats:sup>EC\u2212\/\u2212<\/jats:sup>) mice were intraperitoneally injected with 12\u2009mg\/kg LPS. RSPO3 was intraperitoneally injected 30\u2009min before LPS treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Aerobic exercise\u2010trained mice were more resistant to LPS\u2010induced body weight loss and hypothermia and had a significant higher survival rate than sedentary mice exposed to LPS. Exercise training restored the LPS\u2010induced decreases in serum and renal RSPO3 levels. Exercise or RSPO3 attenuated, whereas inducible endothelial cell\u2010specific RSPO3 knockout exacerbated LPS\u2010induced renal glycocalyx loss, endothelial hyperpermeability, inflammation, and AKI. Bioinformatics analysis results revealed significant increases in the expression of matrix metalloproteinases (MMPs) in kidney tissues of mice exposed to sepsis or endotoxaemia, which was validated in renal tissue from LPS\u2010exposed mice and LPS\u2010treated human microvascular endothelial cells (HMVECs). Both RSPO3 and MMPs inhibitor restored LPS\u2010induced downregulation of tight junction protein, adherens junction protein, and glycocalyx components, thus ameliorating LPS\u2010induced endothelial leakage. Exercise or RSPO3 reversed LPS\u2010induced upregulation of MMPs in renal tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Increased renal expression of RSPO3 contributes to aerobic exercise\u2010induced protection against LPS\u2010induced renal endothelial hyperpermeability and AKI by suppressing MMPs\u2010mediated disruption of glycocalyx and tight and adherens junctions.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.14036","type":"journal-article","created":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T09:28:35Z","timestamp":1692696515000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Increased R\u2010spondin 3 contributes to aerobic exercise\u2010induced protection against renal vascular endothelial hyperpermeability and acute kidney 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