Role of miR-204 in the regulation of apoptosis, endoplasmic reticulum stress response, and inflammation in human trabecular meshwork cells.

Published online

Journal Article

PURPOSE: To investigate the biological functions of miR-204 in human trabecular meshwork (HTM) cells. METHODS: Changes in gene expression induced by miR-204 in HTM cells were evaluated by gene array analysis using arrays and confirmed by quantitative-PCR (Q-PCR). Direct targeting of miR-204 to 12 potential novel targets was confirmed using a luciferase system, and five of them were verified by Western blot analysis. Effects of miR-204 on apoptosis, cell viability, and accumulation of carbonylated proteins were evaluated in HTM cells treated with H(2)O(2). Induction of endoplasmic reticulum (ER) stress markers by tunicamycin was analyzed by Q-PCR, and expression of IL-8 and IL-11 was analyzed by ELISA. RESULTS: MiR-204 decreased the expression of multiple genes in HTM cells. Twelve genes (AP1S2, Bcl2l2, BIRC2, EDEM1, EZR, FZD1, M6PR, RAB22A, RAB40B, SERP1, TCF12, and TCF4) were validated as direct targets of miR-204. Downregulation of expressions at protein levels of Bcl2l2, BIRC2, EZR, M6PR, and SERP1 were confirmed by Western blot analysis. HTM cells transfected with miR-204 showed increased levels of apoptosis, decreased viability, increased accumulation of oxidized proteins after H(2)O(2) treatment, decreased induction of ER stress response markers, and reduced expression of inflammatory mediators IL-8 and IL-11. CONCLUSIONS: MiR-204 potentially plays an important role in the regulation of multiple functions in HTM cells including apoptosis, accumulation of damaged proteins, ER stress response, and expression of inflammatory mediators.

Full Text

Duke Authors

Cited Authors

  • Li, G; Luna, C; Qiu, J; Epstein, DL; Gonzalez, P

Published Date

  • May 6, 2011

Published In

Volume / Issue

  • 52 / 6

Start / End Page

  • 2999 - 3007

PubMed ID

  • 21282569

Electronic International Standard Serial Number (EISSN)

  • 1552-5783

Digital Object Identifier (DOI)

  • 10.1167/iovs.10-6708

Language

  • eng

Conference Location

  • United States