NKILA inhibition protects retinal pigment epithelium cells from hypoxia by facilitating NFκB activation
- Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing (China)
- Department of Ophthalmology, Children's Hospital of Nanjing Medical University, Nanjing (China)
Highlights: • Hypoxia induces NKILA expression in retinal pigment epithelium (RPE) cells. • Hypoxia induces NKILA-IκBα association and NFκB activation in RPE cells. • NKILA shRNA inhibits hypoxia-induced RPE cell death. • NKILA overexpression potentiates hypoxia-induced RPE cell death. • miR-103 inhibition by hypoxia could be a primary reason of NKILA upregulation. Sustained retinal hypoxia causes injuries to retinal pigment epithelium (RPE) cells. We studied expression and potential functions of nuclear factor-κB (NFκB) Interacting LncRNA (NKILA) in hypoxia-treated RPE cells. Hypoxia induced NKILA expression, NKILA-IκBα association and NFκB activation in ARPE-19 cells and primary human RPE cells. shRNA-mediated knockdown of NKILA facilitated NFκB activation, inhibiting RPE cell death and apoptosis. Conversely, exogenous overexpression of NKILA blocked hypoxia-induced NFκB activation, thereby exacerbating RPE cell apoptosis. Further studies show that hypoxia downregulated microRNA-103 (miR-103), the anti-NKILA microRNA, in RPE cells. Transfection of miR-103 mimic blocked hypoxia-induced NKILA expression to significantly boost NFκB activation, protecting RPE cells from hypoxia. Collectively, we conclude that hypoxia-induced NKILA expression negatively regulates NFκB to promote RPE cell death. Conversely, NKILA inhibition protects RPE cells from hypoxia by facilitating NFκB activation.
- OSTI ID:
- 23134246
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 503, Issue 4; Other Information: Copyright (c) 2018 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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