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Abstract #6323 Published in IGR 3-2
Activation of extracellular signal-regulated kinase in trabecular meshwork cells
Shearer T; Crosson CEExperimental Eye Research 2001; 73: 25-35
A number of different agents, such as growth factors, cytokines, and phorbol esters, have been shown to modulate trabecular meshwork cell function. These studies were designed to evaluate the role the extracellular signal-regulated kinase (ERK) pathway plays in mediating the responses to platelet-derived growth factor-BB (PDGF-BB) and phorbol 12-myristate 13-acetate (PMA) in trabecular meshwork cells. The human trabecular meshwork cell line, HTM-3, and the bovine trabecular meshwork (BTM) cells were treated with either PDGF-BB or PMA, and the activation of ERK 1/2 evaluated. The effects of the MAP kinase (MEK) inhibitor U0126, and the PKC inhibitor chelerythrine on ERK 1/2 were also determined. In a separate group of experiments, cells were treated with PDGF-BB or PMA, and the secretion of matrix metalloproteinase-2 (MMP-2) evaluated. The addition or PDGF-BB or PMA produced time- and dose-dependent activation of ERK1/2. Pretreatment with U0126 or chelerythrine significantly reduced ERK1/2 activation induced by PDGF-BB or PMA. The addition of PDGF-BB or PMA stimulated the secretion of MMP-2. This secretory response was inhibited by pretreatment with the MEK inhibitor U0126. In trabecular meshwork cells, PDGF-BB and PMA activate ERK 1/2 by a PKC-dependent mechanism. Activation of ERK 1/2 by these agents in trabecular meshwork cells leads to the secretion of MMP-2. These studies provide evidence that the ERK pathway is an important mechanism for integrating various signals that regulate trabecular function.
Dr T. Shearer, Ola B. Williams Glaucoma Therapeutic Development Center, Department of Ophthalmology, Medical University of South Carolina, Charleston, SC 29425, USA
Classification:
2.5 Meshwork (Part of: 2 Anatomical structures in glaucoma)
4 Tissue culture of ocular cells
