Statins inhibit gliosis of MIO-M1, a Müller glial cell line, induced by TRPV4 activation
- Abstract
- Purpose: We characterized Müller cell gliosis induced by activation of transient receptor potential vanilloid-type 4 (TRPV4) and assessed whether statins could modulate the gliosis.
Methods: The human Müller cell line, used to analyze gliosis caused by glaucomatous stimulation. To induce Müller gliosis in MIO-M1 cells, GSK101 was used to activate TRPV4, and Müller gliosis was evaluated by analyzing vimentin, nestin, and glial fibrillary acidic protein (GFAP) expression. The expression level of TNF-α was determined by ELISA. To evaluate GSK101 activation of the NF-κB pathway, p65 phosphorylation was measured by western blotting, and nuclear translocation of p65 and IκBα phosphorylation were assessed by immunostaining. To assess the effect of statins on MIO-M1 gliosis and its signaling pathway, cells were pretreated for 24 h with simvastatin, atorvastatin, and lovastatin before GSK101 treatment.
Results: Vimentin, nestin, and GFAP expression was upregulated by GSK101 treatment of MIO-M1 cells, confirming gliosis induction. Statins effectively inhibited gliosis. The expression of the cytokine TNF-α, which can induce RGC apoptosis, was increased by GSK101. To investigate the signaling pathway leading to TNF-α expression, NF-κB activation was determined. Phosphorylation and nuclear translocation of p65 and IκBα phosphorylation, which occurs prior to p65 activation, were induced. Statins suppressed GSK101-mediated phosphorylation of IκBα and p65 and p65 translocation.
Conclusions: Statins can mitigate gliosis human Müller cell line. Because TRPV4 activation in Müller cells reflects glaucoma pathophysiology, statins are potential therapeutic agents to prevent RGC death.
- Author(s)
- 조윤혜
- Issued Date
- 2022
- Awarded Date
- 2022-08
- Type
- dissertation
- Keyword
- Glaucoma; Statin; Müller gliosis
- URI
- https://oak.ulsan.ac.kr/handle/2021.oak/9927
http://ulsan.dcollection.net/common/orgView/200000640648
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