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Statins inhibit gliosis of MIO-M1, a Müller glial cell line, induced by TRPV4 activation

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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
GlaucomaStatinMüller gliosis
URI
https://oak.ulsan.ac.kr/handle/2021.oak/9927
http://ulsan.dcollection.net/common/orgView/200000640648
Alternative Author(s)
Youn Hye Jo
Affiliation
울산대학교
Department
일반대학원 의학과
Advisor
성경림
Degree
Doctor
Publisher
울산대학교 일반대학원 의학과
Language
eng
Rights
울산대학교 논문은 저작권에 의해 보호 받습니다.
Appears in Collections:
Medicine > 2. Theses (Ph.D)
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