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Sarah Xin Zhang, Chuangxin Huang, Marek Falkowski, Joshua Jianxin Wang; ERp29 Regulates Cell Stress Response and Tight Junctions in Retinal Pigment Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2329.
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© ARVO (1962-2015); The Authors (2016-present)
Endoplasmic reticulum protein 29 (ERp29) is a novel ER chaperone that was recently reported to be decreased in human retina with age-related macular degeneration (AMD). However, the role of ERp29 in AMD-associated RPE damage is unknown. Herein, we examined the effect of ERp29 on cigarette smoke-induced RPE apoptosis and tight junction disruption.
Cultured human RPE (ARPE-19) cells or mouse RPE eyecup explants were exposed to cigarette smoking extract (CSE) for up to 24 h. Expression of ERp29 was up- or down- regulated by adenovirus or siRNA, respectively. ER stress markers, apoptosis and cell death, the expression and distribution of tight junction protein ZO-1, transepithelial electrical resistance (TEER), and F-actin expression were examined.
ERp29 was significantly increased in ARPE-19 cells or mouse eyecup explants after CSE exposure. Over-expression of ERp29 increased the levels of GRP78, p58IPK and Nrf-2 while reducing p-eIF2α and CHOP expression, and protected RPE cells from CSE-induced apoptosis. In contrast, knockdown of ERp29 decreased the levels of p58IPK and Nrf2 but increased the expression of p-eIF2α and CHOP, and exacerbated CSE-triggered cell death. In addition, over-expression of ERp29 attenuated CSE-induced reduction in ZO-1 expression and enhanced the RPE barrier function measured by TEER, while knockdown of ERp29 decreased the protein level of ZO-1. These effects were associated with changes in cytoskeleton F-actin expression.
Induction of ERp29 by CSE exposure in the RPE attenuates ER stress and enhances cell viability and barrier integrity, and therefore may act as a protective mechanism in RPE survival and activity.
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