Liraglutide Up-regulation Thioredoxin Attenuated Müller Cells Apoptosis in High Glucose by Regulating Oxidative Stress and Endoplasmic Reticulum Stress

ABSTRACT

Purpose: Diabetic retinopathy (DR) has become one of the most important complications of diabetes which is the leading cause of vision impairment and blindness all over the world. Increasing evidence shows that reactive gliosis are basic pathological features of early DR. The study was aimed to explore the protective effect and mechanism of Liraglutide (LIRA) which has similar properties to Glucagon-like peptide-1 (GLP-1) on Müller cell damage induced by diabetes.

Materials and methods: In vitro, the Müller cell was cultured in high glucose (HG) to establish the model of diabetic retinopathy. The apoptosis was detected using flow cytometry. Western blot and immunofluorescence were used to detect the expression of related proteins. DCFH-DA probe was used to detect the ROS generation.

Results: The data showed that the apoptosis and the expression of GFAP were increased significantly with HG treatment. However, the apoptosis percentage and the expression of GFAP were decreased after LIRA treatment. Moreover, the expression of p-Erk/Nrf2/Trx-signaling pathway proteins was also up-regulated and the generation of ROS was decreased after LIRA treatment which was inhibited after treatment with U0126 (Erk inhibitor). Besides, endoplasmic reticulum stress (ER stress) related proteins were up-regulated after Trx down-regulation by transfection with sh-RNA.

Conclusions: LIRA could protect Müller cells from HG-induced damage via activating p-Erk pathway through increasing Trx expression which attenuated oxidative stress and ER stress. Trx could play a key role in the process.

KEYWORDS:

• Liraglutide
• Müller cells
• endoplasmic reticulum stress
• oxidative stress
• thioredoxin

Acknowledgments

We also thank Dr. Hiroshi Masutani (Japan) for providing the Trx-shRNA vectors.

Declaration of interest

None of the authors has any financial/conflicting interests to disclose.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website.

Additional information

Funding

This work was supported by Grant No. [31371218] from the National Natural Science Foundation of China and Grant No. [LQ2017005] from the Basic Scientific Research Projects of Liaoning provincial education department. This work was also supported by Grant NO. [20170540241] from the Natural Science Foundation of Liaoning Province. This work was supported by Liaoning Provincial Program for Top Discipline of Basic Medical Sciences.