{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T19:45:11Z","timestamp":1775504711850,"version":"3.50.1"},"reference-count":39,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,1,17]],"date-time":"2021-01-17T00:00:00Z","timestamp":1610841600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81970639"],"award-info":[{"award-number":["81970639"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recently, the Klotho protein (Klotho) has received substantial attention as protective factor against cardiovascular complications of chronic kidney disease (CKD). However, the direct effect and mechanism of Klotho on endothelial cells injury are not well\u2010known. In this study, we incubated human vein umbilical endothelial cells (HUVECs) with uremic toxin indoxyl sulfate (IS) to mimic CKD internal environment and investigated the direct effect of Klotho on the HUVECs injury induced by IS and to explore the mechanism in this process. We found IS inhibited cell viability, increased endoplasmic reticulum stress, and mediated apoptosis of HUVECs. Treatment with Klotho significantly attenuated IS\u2010induced above effects. Furthermore, Klotho alleviated the IS toxic effect on HUVECs via promoting AMP\u2010activated protein kinase (AMPK) \u03b11 phosphorylation instead of directly upregulating AMPK\u03b11, which could be partly blocked by AMPK pathway inhibitor\u2010Compound C. In addition, Klotho also inhibited intercellular adhesion molecule\u20101 (ICAM\u20101) and vascular cell adhesion molecule\u20101 (VCAM\u20101) expression induced by IS. Altogether, these results indicated that Klotho can protect HUVECs from IS\u2010induced injury by alleviating AMPK\u03b11\u2010mediated endoplasmic reticulum stress.<\/jats:p>","DOI":"10.1002\/jat.4135","type":"journal-article","created":{"date-parts":[[2021,1,17]],"date-time":"2021-01-17T20:25:51Z","timestamp":1610915151000},"page":"1446-1455","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The role of AMP\u2010activated protein kinase \u03b11\u2010mediated endoplasmic reticulum stress in alleviating the toxic effect of uremic toxin indoxyl sulfate on vascular endothelial cells by Klotho"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4509-9273","authenticated-orcid":false,"given":"Cheng","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Nephrology The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital  Nanjing 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