Statins Inhibit the Gliosis of MIO-M1, a Müller Glial Cell Line Induced by TRPV4 Activation
We characterized Müller cell gliosis induced by the activation of transient receptor potential vanilloid-type 4 (TRPV4) and assessed whether statins could modulate the gliosis. The human Müller cell line, MIO-M1, was used to analyze the gliosis caused by glaucomatous stimulation. To induce Müller gl...
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| Format: | Article |
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MDPI AG
2022-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/9/5190 |
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| author | Youn Hye Jo Go Woon Choi Mi-Lyang Kim Kyung Rim Sung |
| author_facet | Youn Hye Jo Go Woon Choi Mi-Lyang Kim Kyung Rim Sung |
| author_sort | Youn Hye Jo |
| collection | DOAJ |
| description | We characterized Müller cell gliosis induced by the activation of transient receptor potential vanilloid-type 4 (TRPV4) and assessed whether statins could modulate the gliosis. The human Müller cell line, MIO-M1, was used to analyze the 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 the GSK101 activation of the NF-κB pathway, p65 phosphorylation was measured by Western blotting, and the nuclear translocation of p65 and IκBα phosphorylation were assessed by immunostaining. To assess the effect of statins on MIO-M1 gliosis, cells were pretreated for 24 h with statins before GSK101 treatment. Vimentin, nestin, and GFAP expression were upregulated by GSK101, while statins effectively inhibited them. The expression of TNF-α was increased by GSK101. The phosphorylation and nuclear translocation of p65 and IκBα phosphorylation, which occurs prior to p65 activation, were induced. Statins suppressed the GSK101-mediated phosphorylation of IκBα and p65 translocation. Statins can mitigate gliosis in the human Müller cell line. Because TRPV4 activation in Müller cells reflects glaucoma pathophysiology, statins may have the potential to prevent RGC death. |
| first_indexed | 2024-03-10T04:03:25Z |
| format | Article |
| id | doaj.art-8760a54f9f684c728428e7117a824174 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T04:03:25Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8760a54f9f684c728428e7117a8241742023-11-23T08:28:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-05-01239519010.3390/ijms23095190Statins Inhibit the Gliosis of MIO-M1, a Müller Glial Cell Line Induced by TRPV4 ActivationYoun Hye Jo0Go Woon Choi1Mi-Lyang Kim2Kyung Rim Sung3Department of Ophthalmology, Konkuk University Medical Center, College of Medicine, Konkuk University, 120, Neungdong-ro, Gwangjin-gu, Seoul 05030, KoreaBiomedical Research Center, Asan Medical Center, College of Medicine, University of Ulsan, 88, Olympic-Ro 43-Gil, Songpa-gu, Seoul 05505, KoreaBiomedical Research Center, Asan Medical Center, College of Medicine, University of Ulsan, 88, Olympic-Ro 43-Gil, Songpa-gu, Seoul 05505, KoreaDepartment of Ophthalmology, Asan Medical Center, College of Medicine, University of Ulsan, 88, Olympic-Ro 43-Gil, Songpa-gu, Seoul 05505, KoreaWe characterized Müller cell gliosis induced by the activation of transient receptor potential vanilloid-type 4 (TRPV4) and assessed whether statins could modulate the gliosis. The human Müller cell line, MIO-M1, was used to analyze the 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 the GSK101 activation of the NF-κB pathway, p65 phosphorylation was measured by Western blotting, and the nuclear translocation of p65 and IκBα phosphorylation were assessed by immunostaining. To assess the effect of statins on MIO-M1 gliosis, cells were pretreated for 24 h with statins before GSK101 treatment. Vimentin, nestin, and GFAP expression were upregulated by GSK101, while statins effectively inhibited them. The expression of TNF-α was increased by GSK101. The phosphorylation and nuclear translocation of p65 and IκBα phosphorylation, which occurs prior to p65 activation, were induced. Statins suppressed the GSK101-mediated phosphorylation of IκBα and p65 translocation. Statins can mitigate gliosis in the human Müller cell line. Because TRPV4 activation in Müller cells reflects glaucoma pathophysiology, statins may have the potential to prevent RGC death.https://www.mdpi.com/1422-0067/23/9/5190glaucomaMüller gliosisNF-κB pathwaystatinTNF-α |
| spellingShingle | Youn Hye Jo Go Woon Choi Mi-Lyang Kim Kyung Rim Sung Statins Inhibit the Gliosis of MIO-M1, a Müller Glial Cell Line Induced by TRPV4 Activation International Journal of Molecular Sciences glaucoma Müller gliosis NF-κB pathway statin TNF-α |
| title | Statins Inhibit the Gliosis of MIO-M1, a Müller Glial Cell Line Induced by TRPV4 Activation |
| title_full | Statins Inhibit the Gliosis of MIO-M1, a Müller Glial Cell Line Induced by TRPV4 Activation |
| title_fullStr | Statins Inhibit the Gliosis of MIO-M1, a Müller Glial Cell Line Induced by TRPV4 Activation |
| title_full_unstemmed | Statins Inhibit the Gliosis of MIO-M1, a Müller Glial Cell Line Induced by TRPV4 Activation |
| title_short | Statins Inhibit the Gliosis of MIO-M1, a Müller Glial Cell Line Induced by TRPV4 Activation |
| title_sort | statins inhibit the gliosis of mio m1 a muller glial cell line induced by trpv4 activation |
| topic | glaucoma Müller gliosis NF-κB pathway statin TNF-α |
| url | https://www.mdpi.com/1422-0067/23/9/5190 |
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