Research Paper Volume 12, Issue 10 pp 9139—9150
Klotho alleviates indoxyl sulfate-induced heart failure and kidney damage by promoting M2 macrophage polarization
- 1 Department of General Practice, Zhejiang Hospital, Hangzhou 310013, Zhejiang, P.R. China
- 2 Department of Critical Care Medicine, Zhejiang Hospital, Hangzhou 310013, Zhejiang, P.R. China
Received: October 29, 2019 Accepted: March 2, 2020 Published: May 28, 2020https://doi.org/10.18632/aging.103183
How to Cite
Copyright © 2020 Lv et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Indoxyl sulfate (IS) is a protein-bound uremic toxin that can accumulate in patients with chronic kidney disease (CKD) or acute kidney injury (AKI) and cause kidney and cardiac dysfunction. Klotho is an anti-aging protein that has reno- and cardio-protective effects. We investigated whether Klotho could alleviate IS-induced heart failure and kidney damage by regulating macrophages, which play a key role in the inflammatory response in CKD and AKI. Treatment of THP-1-derived macrophages with IS induced the production of the pro-inflammatory cytokines TNFα, IL-6, and IL-1β, and stimulated M1 polarization. Additionally, IS induced downregulation of Klotho expression in macrophages. Overexpression of Klotho suppressed the IS-induced inflammatory response in macrophages by stimulating M2 polarization. It also alleviated IS-induced cardiac hypertrophy and renal fibrosis in mice. A reduction in IS-induced phosphorylation of NF-kB p65 was observed in response to Klotho overexpression, suggesting that Klotho alleviates kidney and cardiac injury by inactivating NF-kB signaling and promoting macrophage M2 polarization.