p38 MAP Kinase Inhibitor Suppresses Transforming Growth Factor-[beta]2-Induced Type 1 Collagen Production in Trabecular Meshwork Cells

• Published in: PloS one Vol. 10; no. 3
• Main Authors: Inoue-Mochita, Miyuki, Inoue, Toshihiro, Fujimoto, Tomokazu, Kameda, Takanori, Awai-Kasaoka, Nanako, Ohtsu, Naoki, Kimoto, Kenichi, Tanihara, Hidenobu
• Format: Journal Article
• Language: English
• Published: Public Library of Science 23.03.2015
• Subjects: Bone morphogenetic proteins; Collagen; Glaucoma; Muscle proteins; Myosin; Polymerization; RNA; Transforming growth factors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0120774

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)-[beta]2-induced type I collagen production in human trabecular meshwork cells. TGF-[beta]2 increased RhoA activity, actin polymerization, and myosin light chain 2 phosphorylation. These effects were significantly inhibited by Y-27632, but not SB203580. TGF-[beta]2 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-[beta]2-induced promoter activation, or phosphorylation or nuclear translocation of Smad2/3, whereas SB203580 partially suppressed these processes. Collectively, TGF-[beta]2-induced production of type 1 collagen is suppressed by p38 inhibition and accompanied by partial inactivation of Smad2/3, in human trabecular meshwork cells.