NKILA inhibition protects retinal pigment epithelium cells from hypoxia by facilitating NFκB activation

Journal Article · Sat Sep 15 04:00:00 EDT 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.08.105· OSTI ID:23134246

Zhou, Qing ^[1]; Zhou, Lu; Qian, Jing ^[2]; Yuan, Zhi-lan ^[1]; Chen, Zhi-jun ^[2]

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1. Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing (China)
2. 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, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 503; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANOXIA
APOPTOSIS
EPITHELIUM
INJURIES
RHODOPSIN