Yonsei Med J.  2003 Apr;44(2):299-306. 10.3349/ymj.2003.44.2.299.

Cellular Proliferative Effect of Dexamethasone in Immortalized Trabecular Meshwork Cell (TM5) Line

• Jeon JW
• Lee SJ
• Kim JB
• Kang JJ
• Lee JH
• Seong GJ
• Kim EK

• KMID: 1779480
• DOI: http://doi.org/10.3349/ymj.2003.44.2.299

Abstract

Dexamethasone (DEX), one of the corticosteroid hormones, is one of the most common therapeutic strategies in ophthalmological treatment. Despite its widespread use and clinical efficiency, little is known regarding the specific effects of DEX on cell growth, differentiation and cell death in human trabecular meshwork cells. The presence of the glucocorticoid receptor (GR, dexamethasone receptor) in TM-5 cell line, which was derived from the primary human trabecular meshwork cells, was verified by RT-PCR and western blot analysis. The effects of DEX on the cellular proliferation of TM5 cells were measured by a BrdU incorporation assay. Western blot analysis were used to examine the effects of DEX on the Ras/MEK/ERK signaling pathway. The total Ras, MEK1/2 and ERK1/2 protein levels as well as the levels of activated (phosphorylated) form were both significantly increased by the DEX treatment for 5 days. Both MEK1/2 and ERK1/2 were significantly activated by phosphorylation after 10 minutes. The dependence of this increased cell proliferation on GR activation by DEX and the sustained activation of ERK was examined using RU486 (a GR inhibitor) and U0126 (a MEK inhibitor). Both RU486 and U0126 prevented the induction of cell proliferation by the DEX treatment in the TM5 cells. In conclusion this study demonstrated that GR is expressed in TM5 cells. Secondly, DEX treatment for 5 days stimulates cell proliferation in TM5 cells, and that this increased proliferation effect is mediated by the Ras/MEK/ERK pathway.

Keyword

Dexamethasone; glucocorticoid receptor; MAPK pathway; cell proliferation; human trabecular meshwork cells

MeSH Terms

Cell Division/*drug effects
Cells, Cultured
Dexamethasone/*pharmacology
Human
Mitogen-Activated Protein Kinase Kinases/metabolism
Mitogen-Activated Protein Kinases/metabolism
Protein-Serine-Threonine Kinases/metabolism
Protein-Tyrosine Kinase/metabolism
Proto-Oncogene Proteins c-raf/metabolism
Receptors, Glucocorticoid/physiology
Trabecular Meshwork/cytology/*drug effects