Work

Klotho alleviates contrast-induced acute kidney injury by suppressing oxidative stress, inflammation, and NF-KappaB/NLRP3-mediated pyroptosis

Year: 2023

Type: article

Abstract: Background Contrast-induced acute kidney injury (CI-AKI) is a common complication following percutaneous coronary intervention in coronary artery disease (CAD) patients with more than 30% incidence. Klotho is a multifunctional protein that inhibits oxidative stress and inflammation, but its role in CI-AKI is poorly understood. The present study aimed to explore the effects of klohto in CI-AKI. Methods Six-week-old mice and HK-2 were divided into control group, contrast medium (CM) group, CM + klotho group, and klotho group. Kidney injury was evaluated by HE staining. And the renal function was shown by Scr and BUN. Cell viability and damage were determined by CCK-8 assay and lactate dehydrogenase (LDH) activity assay. Oxidative stress related indicators including intracellular reactive oxygen species (ROS), superoxidase dismutase (SOD), and malondialdehyde (MDA) were tested by fluorescent probe dichloro-dihydro-fluorescein diacetate (DCFH-DA) and enzyme-linked immunosorbent assay (ELISA) assay. IL-6, TNF-α, IL-1β, and IL-18 in the cell supernatant were tested by ELISA assay and used to reflect inflammation responses. Propidium iodide (PI) staining showed the cell death of HK-2. The expression of NF-κB, phosphorylated NF-κB (p-NF-κB), and pyroptosis-related protein levels of NLRP3, caspase-1, GSDMD, and cleaved-GSDMD were detected by western blot. Results Exogenous Klotho administration reduced kidney histopathological alterations and improved renal function in vivo. In vitro, Klotho significantly inhibited CM-induced oxidative stress and productions of both IL-6 and TNF-α. Moreover, we found klotho inhibited the activation of p-NF-κB and down-regulated pyroptosis-related protein (NLRP3, caspase-1, GSDMD, and cleaved-GSDMD). Conclusion The findings suggested that klotho had a protective effect on CI-AKI via suppressing oxidative stress, inflammation and NF-κB/NLRP3-mediated pyroptosis, contributing to the potential therapy of CI-AKI.

Source: International Immunopharmacology

DOI: 10.1016/j.intimp.2023.110105

Authors: Yanbin Fu, Jianfeng Cao, Xuebiao Wei, Yanzhi Ge, Zedazhong Su, Danqing Yu

Institutions: Guangdong Academy of Medical Sciences, Guangdong Provincial People's Hospital, Southern Medical University, Zhejiang Chinese Medical University

Language: English

Topic: Acute Kidney Injury Research

Subfield: Nephrology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green