title: The selective cysteinyl leukotriene receptor 1 (CysLT1R) antagonist montelukast regulates extracellular matrix remodeling.
abstract: Scar formation after filtration surgery of glaucoma is mainly caused by excessive synthesis of new extracellular matrix (ECM) and contraction of subconjunctival tissue mediated by human Tenon fibroblasts (HTFs) and the transforming growth factor (TGF-β1). Montelukast, a potent and specific cysteinyl leukotriene receptor 1 (cysLT1R) antagonist, is a licensed drug clinically used for the treatment of bronchial asthma. In this study, we investigated the effects of montelukast on the contractility of HTFs cultured in a three-dimensional collagen gel. We found that cysLT1R was expressed in HTFs. Interestingly, the expression of cysLT1R was increased in response to TGF-β1 in a dose dependent manner, suggesting its potential role in TGF-β1 induced fibrosis. Importantly, we found that montelukast inhibited TGF-β1-induced collagen gel contraction mediated by HTFs in a concentration- and time-dependent manner. In addition, TGF-β1-induced expression of MMP-1 and MMP-3, generation of fibronectin and type I collagen production, focal adhesion kinase (FAK) and paxillin phosphorylation in HTFs were also ameliorated by montelukast in a dose dependent manner. These results suggested that montelukast might provide therapeutic possibilities for inhibition of scar formation after such surgery.
authors.affiliation: Department of Ophthalmology, Wuhan General Hospital of Guangzhou Command, Southern Medical University, Wuhan, Hubei Province, 430000, China; Department of Ophthalmology, Chenzhou First People's Hospital, Chenzhou, Hunan Province, 430000, China.
authors.forename: Jingli
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Ophthalmology, Wuhan General Hospital of Guangzhou Command, Southern Medical University, Wuhan, Hubei Province, 430000, China. Electronic address: hezzhou998@yeah.net.
authors.forename: Hezheng
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Ophthalmology, Chenzhou First People's Hospital, Chenzhou, Hunan Province, 430000, China.
authors.forename: Guoping
authors.initials: G
authors.lastname: Kuang
authors.affiliation: Department of Ophthalmology, Chenzhou First People's Hospital, Chenzhou, Hunan Province, 430000, China.
authors.forename: Lilian
authors.initials: L
authors.lastname: Xie
authors.affiliation: Department of Ophthalmology, Chenzhou First People's Hospital, Chenzhou, Hunan Province, 430000, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Tian
authors.affiliation: Department of Ophthalmology, Chenzhou First People's Hospital, Chenzhou, Hunan Province, 430000, China.
authors.forename: Ru
authors.initials: R
authors.lastname: Liu
mesh_terms: D000085:Acetates / Q000008:administration & dosage*; D002478:Cells, Cultured; D003521:Cyclopropanes; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006801:Humans; D020024:Leukotriene Antagonists / Q000008:administration & dosage*; D011804:Quinolines / Q000008:administration & dosage*; D018077:Receptors, Leukotriene / Q000187:drug effects* / Q000378:metabolism; D013440:Sulfides; D000070916:Tenocytes / Q000187:drug effects / Q000378:metabolism*; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
chemical_list: D000085:Acetates; D003521:Cyclopropanes; D016326:Extracellular Matrix Proteins; D020024:Leukotriene Antagonists; D011804:Quinolines; D018077:Receptors, Leukotriene; D013440:Sulfides; C083169:leukotriene D4 receptor; C093875:montelukast
keywords: Cysteinyl leukotrienes; Montelukast; Tenon fibroblasts; Transforming growth factor-β1; Wound healing