Activation of Prostaglandin FP and EP2 Receptors Differently Modulates Myofibroblast Transition in a Model of Adult Primary Human Trabecular Meshwork Cells

Autor: Stéphane Mélik-Parsadaniantz, Michael Bakria, Thomas Debeir, William Rostène, Fanny Beguier, Caroline Leriche, Xavier Vigé, Georges Kalouche, Christophe Baudouin
Rok vydání: 2016
Předmět:
0301 basic medicine
Adult
Male
Prostaglandins E
Synthetic
medicine.medical_specialty
Myosin light-chain kinase
Myosin Light Chains
genetic structures
Cell Survival
Prostaglandin E2 receptor
Blotting
Western
Receptors
Prostaglandin
Prostaglandin
macromolecular substances
Dinoprost
Real-Time Polymerase Chain Reaction
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Trabecular Meshwork
Internal medicine
medicine
Animals
Humans
Alprostadil
Receptor
Myofibroblasts
Actin
Antihypertensive Agents
Cells
Cultured
Glaucoma
Receptors
Prostaglandin E
EP2 Subtype
Immunohistochemistry
Actins
Cell biology
Rats
030104 developmental biology
Endocrinology
medicine.anatomical_structure
Neuroprotective Agents
chemistry
Prostaglandins F
Synthetic
030221 ophthalmology & optometry
Latanoprost
RNA
Trabecular meshwork
Signal transduction
Myofibroblast
Signal Transduction
Zdroj: Investigative ophthalmologyvisual science. 57(4)
ISSN: 1552-5783
Popis: Purpose Prostaglandin F2α analogues are the first-line medication for the treatment of ocular hypertension (OHT), and prostanoid EP2 receptor agonists are under clinical development for this indication. The goal of this study was to investigate the effects of F prostanoid (FP) and EP2 receptor activation on the myofibroblast transition of primary trabecular meshwork (TM) cells, which could be a causal mechanism of TM dysfunction in glaucoma. Methods Human primary TM cells were treated with either latanoprost or butaprost and TGF-β2. Trabecular meshwork contraction was measured in a three-dimensional (3D) TM cell-populated collagen gel (CPCG) model. Expression of α-smooth muscle actin (α-SMA) and phosphorylation of myosin light chain (MLC) were determined by Western blot. Assembly of actin stress fibers and collagen deposition were evaluated by immunocytochemistry. Involvement of p38, extracellular signal-regulated kinase (ERK), and Rho-associated kinase (ROCK) pathways as well as matrix metalloproteinase activation was tested with specific inhibitors. Results In one source of validated adult TM cells, latanoprost induced cell contraction as observed by CPCG surface reduction and increased actin polymerization, α-SMA expression, and MLC phosphorylation, whereas butaprost inhibited TGF-β2-induced CPCG contraction, actin polymerization, and MLC phosphorylation. Both agonists inhibited TGF-β2-dependent collagen deposition. The latanoprost effects were mediated by p38 pathway. Conclusions Latanoprost decreased TM collagen accumulation but promoted a contractile phenotype in a source of adult TM cells that could modulate the conventional outflow pathway. In contrast, butaprost attenuated both TM contraction and collagen deposition induced by TGF-β2, thereby inhibiting myofibroblast transition of TM cells. These results open new perspectives for the management of OHT.
Databáze: OpenAIRE
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