Inoue-Mochita Miyuki, Inoue Toshihiro, Fujimoto Tomokazu, Kameda Takanori, Awai-Kasaoka Nanako, Ohtsu Naoki, Kimoto Kenichi, Tanihara Hidenobu
Department of Ophthalmology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Department of Ophthalmology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto.
PLoS One. 2015 Mar 23;10(3):e0120774. doi: 10.1371/journal.pone.0120774. eCollection 2015.
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.
青光眼是一种与年龄相关的视网膜神经节细胞神经退行性疾病，小梁网中细胞外基质的适当更新在其病理过程中很重要。在此，我们报告了Rho相关激酶（ROCK）和p38丝裂原活化蛋白激酶对转化生长因子（TGF）-β2诱导的人小梁网细胞中I型胶原蛋白产生的影响。TGF-β2增加了RhoA活性、肌动蛋白聚合和肌球蛋白轻链2磷酸化。这些作用被Y-27632显著抑制，但未被SB203580抑制。TGF-β2还增加了COL1A2的启动子活性、mRNA合成和蛋白质表达。这些作用被SB203580显著抑制，但未被Y-27632抑制。此外，Y-27632并未显著抑制TGF-β2诱导的启动子激活，或Smad2/3的磷酸化或核转位，而SB203580部分抑制了这些过程。总体而言，在人小梁网细胞中，p38抑制可抑制TGF-β2诱导的I型胶原蛋白产生，并伴有Smad2/3的部分失活。
