Skip to main content
main-content

24.09.2018 | Laboratory Investigation | Ausgabe 6/2018

Japanese Journal of Ophthalmology 6/2018

Contribution of the clock gene DEC2 to VEGF mRNA upregulation by modulation of HIF1α protein levels in hypoxic MIO-M1 cells, a human cell line of retinal glial (Müller) cells

Zeitschrift:
Japanese Journal of Ophthalmology > Ausgabe 6/2018
Autoren:
Naoki Kusunose, Takahiro Akamine, Yoshiyuki Kobayashi, Shigeo Yoshida, Kenichi Kimoto, Sai Yasukochi, Naoya Matsunaga, Satoru Koyanagi, Shigehiro Ohdo, Toshiaki Kubota
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s10384-018-0622-5) contains supplementary material, which is available to authorized users.
Corresponding author: Naoki Kusunose

Abstract

Purpose

Clock genes are components of the molecular clock. Their malfunction is thought to increase the risk of numerous diseases, including cancer. Vascular endothelial growth factor (VEGF) has a pivotal role in angiogenesis, and its expression levels are controlled by clock genes in tumor cells. Ophthalmic diseases such as age-related macular degeneration, proliferative diabetic retinopathy, and neovascular glaucoma are also associated with abnormal angiogenesis followed by upregulation of VEGF in the eye. In the present study, we aimed to uncover the relationship between clock genes and VEGF in the eye.

Study design

Laboratory investigation

Methods

Oxygen-induced retinopathy (OIR) mice were prepared to mimic hypoxic conditions in the eye. Deferoxamine (DFO) was used to mimic hypoxic conditions in human Müller cell line MIO-M1 cells. Expression levels of mRNA and protein were quantified by quantitative reverse transcription polymerase chain reaction and Western blot analysis, respectively.

Results

In the retinas of OIR mice, the expression levels of Vegf and the clock gene Dec2 increased transiently, and their temporal profiles were correlated. Knockdown of DEC2 resulted in a significant (26.7%) reduction of VEGF expression in MIO-M1 cells under hypoxia-mimicking conditions induced by DFO (P < .05). Levels of HIF1α protein were also reduced significantly, by 60.2%, in MIO-M1 cells treated with siRNA against the DEC2 gene (P < .05). Moreover, HIF1α levels showed a significant (2.5-fold) increase in MIO-M1 cells overexpressing DEC2 (P < .05).

Conclusion

DEC2 could upregulate retinal VEGF gene expression through modulation of HIF1α levels under hypoxic conditions.

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

★ PREMIUM-INHALT
e.Med Interdisziplinär

Für Ihren Erfolg in Klinik und Praxis - Die beste Hilfe in Ihrem Arbeitsalltag als Mediziner

Mit e.Med Interdisziplinär erhalten Sie Zugang zu allen CME-Fortbildungen und Fachzeitschriften auf SpringerMedizin.de.

Zusatzmaterial
Nur für berechtigte Nutzer zugänglich
Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 6/2018

Japanese Journal of Ophthalmology 6/2018 Zur Ausgabe

Scientific Reviewers

Scientific Reviewers

Neu im Fachgebiet Augenheilkunde