title: p38 MAP kinase inhibitor suppresses transforming growth factor-β2-induced type 1 collagen production in trabecular meshwork cells.
abstract: 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.
authors: Department of Ophthalmology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors: Miyuki
authors: M
authors: Inoue-Mochita
authors: Department of Ophthalmology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors: Toshihiro
authors: T
authors: Inoue
authors: Department of Ophthalmology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors: Tomokazu
authors: T
authors: Fujimoto
authors: Department of Ophthalmology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto.
authors: Takanori
authors: T
authors: Kameda
authors: Department of Ophthalmology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors: Nanako
authors: N
authors: Awai-Kasaoka
authors: Department of Ophthalmology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors: Naoki
authors: N
authors: Ohtsu
authors: Department of Ophthalmology, Oita University, Yufu, Japan.
authors: Kenichi
authors: K
authors: Kimoto
authors: Department of Ophthalmology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors: Hidenobu
authors: H
authors: Tanihara
mesh_terms: D024722:Cardiac Myosins / Q000378:metabolism; D002460:Cell Line; D024042:Collagen Type I / Q000096:biosynthesis*; D006801:Humans; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism; D014129:Trabecular Meshwork / Q000166:cytology* / Q000378:metabolism*; D053781:Transforming Growth Factor beta2 / Q000378:metabolism* / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D018994:Myosin Light Chains; D047428:Protein Kinase Inhibitors; D051785:Smad Proteins; D053781:Transforming Growth Factor beta2; C107184:myosin light chain 2; D054460:rho-Associated Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D024722:Cardiac Myosins