100 107

Cited 0 times in

The Effect of CHIR 99021, a Glycogen Synthase Kinase-3β Inhibitor, on Transforming Growth Factor β-Induced Tenon Fibrosis

Authors
 Sang Yeop Lee  ;  Min Kyoung Chae  ;  Jin Sook Yoon  ;  Chan Yun Kim 
Citation
 INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Vol.62(15) : 25, 2021-12 
Journal Title
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
ISSN
 0146-0404 
Issue Date
2021-12
MeSH
Actins / metabolism ; Blotting, Western ; Cells, Cultured ; Collagen Type I, alpha 1 Chain / metabolism ; Enzyme Inhibitors / pharmacology* ; Fibroblasts / metabolism ; Fibronectins / metabolism ; Fibrosis ; Glycogen Synthase Kinase 3 beta / antagonists & inhibitors* ; Humans ; Pyridines / pharmacology* ; Pyrimidines / pharmacology* ; Real-Time Polymerase Chain Reaction ; Tenon Capsule / drug effects* ; Tenon Capsule / enzymology ; Tenon Capsule / pathology* ; Transforming Growth Factor beta / pharmacology*
Abstract
Purpose: This study investigated the effect of glycogen synthase kinase-3β (GSK-3β) inhibition on the fibrosis of human Tenon's fibroblasts (HTFs) induced by transforming growth factor-β (TGF-β).

Methods: Quantitative real-time PCR and Western blot analyses were performed to determine the expression levels of molecules associated with the fibrosis of HTFs by TGF-β (fibronectin, collagen Iα, and α-smooth muscle actin) and GSK-3β. The levels of phosphorylated Smad2 and Smad3 were also analyzed in the presence of the GSK-3β inhibitor CHIR 99021. The wound healing assay was performed to determine the effect of CHIR 99021 on the migration of HTFs. All experiments were conducted using primary cultured HTFs or human tenon tissues obtained from normal subjects and patients with glaucoma.

Results: Treatment with TGF-β resulted in an increase in the levels of molecules associated with the fibrosis of HTFs. The expression levels of these molecules were higher in the tenon tissues obtained from patients with glaucoma than those from normal subjects. When the HTFs were treated with TGF-β, a significant increase in the active form of GSK-3β (Y216) was observed. A significant decrease in the active form of GSK-3β and molecules associated with fibrosis by TGF-β was noted in HTFs treated with CHIR 99021. CHIR 99021 treatment reduced the phosphorylated Smad2/Smad2 and phosphorylated Smad3/Smad3 ratios in HTFs and attenuated HTF migration.

Conclusions: Our results demonstrated the effect of GSK-3β inhibition on the regulation of TGF-β-mediated fibrosis of HTFs, suggesting GSK-3β to be a potential target for maintaining bleb function after glaucoma filtration surgery.
Files in This Item:
T202124864.pdf Download
DOI
10.1167/iovs.62.15.25
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Chan Yun(김찬윤) ORCID logo https://orcid.org/0000-0002-8373-9999
Yoon, Jin Sook(윤진숙) ORCID logo https://orcid.org/0000-0002-8751-9467
Lee, Sang Yeop(이상엽) ORCID logo https://orcid.org/0000-0002-3834-7953
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/187563
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links