Niclosamide Inhibits Aortic Valve Interstitial Cell Calcification by Interfering with the GSK-3β/β-Catenin Signaling Pathway
10.4062/biomolther.2022.146
- Author:
Radhika ADHIKARI
1
;
Saugat SHIWAKOTI
;
Eunmin KIM
;
Ik Jun CHOI
;
Sin-Hee PARK
;
Ju-Young KO
;
Kiyuk CHANG
;
Min-Ho OAK
Author Information
1. College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Muan 58554, Republic of Korea
- Publication Type:Original Article
- From:Biomolecules & Therapeutics
2023;31(5):515-525
- CountryRepublic of Korea
- Language:English
-
Abstract:
The most common heart valve disorder is calcific aortic valve stenosis (CAVS), which is characterized by a narrowing of the aortic valve. Treatment with the drug molecule, in addition to surgical and transcatheter valve replacement, is the primary focus of researchers in this field. The purpose of this study is to determine whether niclosamide can reduce calcification in aortic valve interstitial cells (VICs). To induce calcification, cells were treated with a pro-calcifying medium (PCM). Different concentrations of niclosamide were added to the PCM-treated cells, and the level of calcification, mRNA, and protein expression of calcification markers was measured. Niclosamide inhibited aortic valve calcification as observed from reduced alizarin red s staining in niclosamide treated VICs and also decreased the mRNA and protein expressions of calcification-specific markers: runt-related transcription factor 2 and osteopontin. Niclosamide also reduced the formation of reactive oxygen species, NADPH oxidase activity and the expression of Nox2 and p22 phox . Furthermore, in calcified VICs, niclosamide inhibited the expression of β-catenin and phosphorylated glycogen synthase kinase (GSK-3β), as well as the phosphorylation of AKT and ERK. Taken together, our findings suggest that niclosamide may alleviate PCM-induced calcification, at least in part, by targeting oxidative stress mediated GSK-3β/β-catenin signaling pathway via inhibiting activation of AKT and ERK, and may be a potential treatment for CAVS.
