Regulation of inflammation by VEGF/BDNF signaling in mouse retinal Müller glial cells exposed to high glucose.

Abstract

The inflammatory changes seem to play an important role in the development of diabetic retinopathy (DR). Anti-VEGF therapy has been testified to inhibit inflammation in animal models of diabetes, but the detailed mechanisms during this process are not yet clear. Müller glial cells (MGCs) in the mammalian retina are deeply involved in DR, while the BDNF overexpression reduces inflammation in diabetic mice. In this research, we aimed to explore the relationship between VEGF and BDNF in mouse retinal MGCs during inflammation of diabetes. We examined the expression of glutamine-synthetase (GS), glial fibrillary acidic protein (GFAP), vascular-endothelial growth factor (VEGF), interleukin-1beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) at different time points after mouse retinal MGCs exposed to high glucose (25 mM). We also explored changes in the expression of brain-derived neurotrophic factor (BDNF), nuclear factor kappa B (NF-κB), IL-1β, and TNF-α in MGCs after treatments with anti-VEGF, VEGF siRNA, BDNF siRNA, BDNF recombination protein, and NF-κB inhibitor. In mouse retinal MGCs exposed to high glucose, BDNF was increased after treatments with anti-VEGF or VEGF siRNA. BDNF was decreased in MGCs from VEGF overexpressed mice. Moreover, the expressions of NF-κB, IL-1β, and TNF-α changed with BDNF: NF-κB, IL-1β, and TNF-α were increased after treatments with BDNF siRNA; NF-κB, IL-1β, and TNF-α were decreased after treatments with BDNF recombination protein. VEGF may regulate cytokines (IL-1β and TNF-α) by BDNF/NF-κB signaling pathway. The regulation of the VEGF/BDNF/NF-κB signaling pathway may be a significant therapeutic strategy for DR.

• Authors: Minqi Zhu, Na Li, Yanuo Wang, Shuang Gao, Jing Wang, Xi Shen
• Journal: Cell and tissue research (Cell Tissue Res) Vol. 388 Issue 3 Pg. 521-533 (Jun 2022) ISSN: 1432-0878 [Electronic] Germany
• PMID: 35394215 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Chemical References

• Brain-Derived Neurotrophic Factor
• NF-kappa B
• RNA, Small Interfering
• Tumor Necrosis Factor-alpha
• Vascular Endothelial Growth Factor A
• Glucose

Topics

• Animals
• Brain-Derived Neurotrophic Factor
• Diabetes Mellitus, Experimental (drug therapy)
• Diabetic Retinopathy (drug therapy)
• Ependymoglial Cells (pathology)
• Glucose (pharmacology)
• Inflammation
• Mammals (metabolism)
• Mice
• NF-kappa B (metabolism)
• RNA, Small Interfering
• Signal Transduction
• Tumor Necrosis Factor-alpha (metabolism)
• Vascular Endothelial Growth Factor A (metabolism)