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Abstract #112420 Published in IGR 24-3
Niclosamide inhibits TGF-β1-induced fibrosis of human Tenon's fibroblasts by regulating the MAPK-ERK1/2 pathway
Zhang L; Li W; Liu X; Guo J; Wu X; Wang JExperimental Eye Research 2023; 235: 109628
Preventing postoperative bleb scar formation is an effective way of improving glaucoma filtration surgery (GFS) outcome. Use of more effective antifibrotic drugs with fewer adverse effects may be a good way to address the problem. In the present study, we use a primary cell model, consisting of Tenon's fibroblasts obtained from patients with glaucoma, which were stimulated with TGF-β1 to induce the fibrotic phenotype. We explored the effects of niclosamide on TGF-β1-induced fibrosis in these cells and examined its underlying mechanism of action. A transcriptome sequencing assay was used to explore possible signaling pathways involved. Niclosamide inhibited cell proliferation and migration, and decreased the levels of alpha-smooth muscle actin, type I and type III collagen in human Tenon's fibroblasts induced by TGF-β1. Niclosamide also induced apoptosis and counteracted TGF-β1-induced cytoskeletal changes and extracellular matrix accumulation. Moreover, niclosamide decreased TGF-β1-induced phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) protein expression in human Tenon's fibroblasts. The results indicate that niclosamide inhibits TGF-β1-induced fibrosis in human Tenon's fibroblasts by blocking the MAPK-ERK1/2 signaling pathway. Thus, niclosamide is a potentially promising antifibrotic drug that could improve glaucoma filtration surgery success rate.
Jinzhou Medical University, Jinzhou, 121001, Liaoning, China.
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