1. Academic Validation
  2. Niclosamide inhibits TGF-β1-induced fibrosis of human Tenon's fibroblasts by regulating the MAPK-ERK1/2 pathway

Niclosamide inhibits TGF-β1-induced fibrosis of human Tenon's fibroblasts by regulating the MAPK-ERK1/2 pathway

  • Exp Eye Res. 2023 Aug 22;109628. doi: 10.1016/j.exer.2023.109628.
Liyun Zhang 1 Wei Li 2 Xin Liu 3 Junhong Guo 3 Xueping Wu 1 Jiantao Wang 4
Affiliations

Affiliations

  • 1 Jinzhou Medical University, Jinzhou, 121001, Liaoning, China.
  • 2 Department of Pediatric Pulmonology, Maternal and Child Health Hospital of Hubei Province, Wuhan, 430070, Hubei, China.
  • 3 Shenzhen Eye Hospital, Jinan University, Shenzhen Eye Institute, Shenzhen, 518000, Guangdong, China.
  • 4 Shenzhen Eye Hospital, Jinan University, Shenzhen Eye Institute, Shenzhen, 518000, Guangdong, China. Electronic address: wangjiantao65@126.com.
Abstract

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.

Keywords

Antifibrosis; ERK1/2; Glaucoma; Human Tenon's capsule fibroblasts; Niclosamide; Transforming growth factor-β1.

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