p38 MAP kinase inhibitor suppresses transforming growth factor-β2-induced type 1 collagen production in trabecular meshwork cells.
Glaucoma is an age-related neurodegenerative disease of retinal ganglion cells, and appropriate turnover of the extracellular matrix in the trabecular meshwork is important in its pathology. Here, we report the effects of Rho-associated kinase (ROCK) and p38 MAP kinase on transforming growth factor...
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Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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Series: | PLoS ONE |
Online Access: | https://doi.org/10.1371/journal.pone.0120774 |
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author | Miyuki Inoue-Mochita Toshihiro Inoue Tomokazu Fujimoto Takanori Kameda Nanako Awai-Kasaoka Naoki Ohtsu Kenichi Kimoto Hidenobu Tanihara |
author_facet | Miyuki Inoue-Mochita Toshihiro Inoue Tomokazu Fujimoto Takanori Kameda Nanako Awai-Kasaoka Naoki Ohtsu Kenichi Kimoto Hidenobu Tanihara |
author_sort | Miyuki Inoue-Mochita |
collection | DOAJ |
description | Glaucoma is an age-related neurodegenerative disease of retinal ganglion cells, and appropriate turnover of the extracellular matrix in the trabecular meshwork is important in its pathology. Here, we report the effects of Rho-associated kinase (ROCK) and p38 MAP kinase on transforming growth factor (TGF)-β2-induced type I collagen production in human trabecular meshwork cells. TGF-β2 increased RhoA activity, actin polymerization, and myosin light chain 2 phosphorylation. These effects were significantly inhibited by Y-27632, but not SB203580. TGF-β2 also increased promoter activity, mRNA synthesis, and protein expression of COL1A2. These effects were significantly inhibited by SB203580, but not Y-27632. Additionally, Y-27632 did not significantly inhibit TGF-β2-induced promoter activation, or phosphorylation or nuclear translocation of Smad2/3, whereas SB203580 partially suppressed these processes. Collectively, TGF-β2-induced production of type 1 collagen is suppressed by p38 inhibition and accompanied by partial inactivation of Smad2/3, in human trabecular meshwork cells. |
first_indexed | 2024-12-21T06:03:44Z |
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id | doaj.art-98b38f90f60c41f0b067d009828ee6c9 |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-12-21T06:03:44Z |
publishDate | 2015-01-01 |
publisher | Public Library of Science (PLoS) |
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series | PLoS ONE |
spelling | doaj.art-98b38f90f60c41f0b067d009828ee6c92022-12-21T19:13:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01103e012077410.1371/journal.pone.0120774p38 MAP kinase inhibitor suppresses transforming growth factor-β2-induced type 1 collagen production in trabecular meshwork cells.Miyuki Inoue-MochitaToshihiro InoueTomokazu FujimotoTakanori KamedaNanako Awai-KasaokaNaoki OhtsuKenichi KimotoHidenobu TaniharaGlaucoma is an age-related neurodegenerative disease of retinal ganglion cells, and appropriate turnover of the extracellular matrix in the trabecular meshwork is important in its pathology. Here, we report the effects of Rho-associated kinase (ROCK) and p38 MAP kinase on transforming growth factor (TGF)-β2-induced type I collagen production in human trabecular meshwork cells. TGF-β2 increased RhoA activity, actin polymerization, and myosin light chain 2 phosphorylation. These effects were significantly inhibited by Y-27632, but not SB203580. TGF-β2 also increased promoter activity, mRNA synthesis, and protein expression of COL1A2. These effects were significantly inhibited by SB203580, but not Y-27632. Additionally, Y-27632 did not significantly inhibit TGF-β2-induced promoter activation, or phosphorylation or nuclear translocation of Smad2/3, whereas SB203580 partially suppressed these processes. Collectively, TGF-β2-induced production of type 1 collagen is suppressed by p38 inhibition and accompanied by partial inactivation of Smad2/3, in human trabecular meshwork cells.https://doi.org/10.1371/journal.pone.0120774 |
spellingShingle | Miyuki Inoue-Mochita Toshihiro Inoue Tomokazu Fujimoto Takanori Kameda Nanako Awai-Kasaoka Naoki Ohtsu Kenichi Kimoto Hidenobu Tanihara p38 MAP kinase inhibitor suppresses transforming growth factor-β2-induced type 1 collagen production in trabecular meshwork cells. PLoS ONE |
title | p38 MAP kinase inhibitor suppresses transforming growth factor-β2-induced type 1 collagen production in trabecular meshwork cells. |
title_full | p38 MAP kinase inhibitor suppresses transforming growth factor-β2-induced type 1 collagen production in trabecular meshwork cells. |
title_fullStr | p38 MAP kinase inhibitor suppresses transforming growth factor-β2-induced type 1 collagen production in trabecular meshwork cells. |
title_full_unstemmed | p38 MAP kinase inhibitor suppresses transforming growth factor-β2-induced type 1 collagen production in trabecular meshwork cells. |
title_short | p38 MAP kinase inhibitor suppresses transforming growth factor-β2-induced type 1 collagen production in trabecular meshwork cells. |
title_sort | p38 map kinase inhibitor suppresses transforming growth factor β2 induced type 1 collagen production in trabecular meshwork cells |
url | https://doi.org/10.1371/journal.pone.0120774 |
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