ArticleJournal of applied toxicology : JAT2021
The role of AMP-activated protein kinase α1-mediated endoplasmic reticulum stress in alleviating the toxic effect of uremic toxin indoxyl sulfate on vascular endothelial cells by Klotho.
Article in Journal of applied toxicology : JAT, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.
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Who cites it
5 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.
- Impact of Uremic Toxins on Endothelial Dysfunction in Chronic Kidney Disease: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- Bridging gut microbiota and renal health: Klotho as a promising therapeutic agent in DKD.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
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- The role of AMP-activated protein kinase α1-mediated endoplasmic reticulum stress in alleviating the toxic effect of uremic toxin indoxyl sulfate on vascular endothelial cells by Klotho.Journal of applied toxicology : JAT · 2021Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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-known. 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-induced above effects. Furthermore, Klotho alleviated the IS toxic effect on HUVECs via promoting AMP-activated protein kinase (AMPK) α1 phosphorylation instead of directly upregulating AMPKα1, which could be partly blocked by AMPK pathway inhibitor-Compound C. In addition, Klotho also inhibited intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression induced by IS. Altogether, these results indicated that Klotho can protect HUVECs from IS-induced injury by alleviating AMPKα1-mediated endoplasmic reticulum stress.
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