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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Main Authors: Miyuki Inoue-Mochita, Toshihiro Inoue, Tomokazu Fujimoto, Takanori Kameda, Nanako Awai-Kasaoka, Naoki Ohtsu, Kenichi Kimoto, Hidenobu Tanihara
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
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.
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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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