p38 MAP kinase inhibitor suppresses transforming growth factor-β2-induced type 1 collagen production in trabecular meshwork cells.
p38 MAP kinase inhibitor suppresses transforming growth factor-β2-induced type 1 collagen production in trabecular meshwork cells.
复制标题
DOI：
10.1371/journal.pone.0120774
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Tanihara H
中科院分区：
文献类型：
--
作者：
Inoue-Mochita M;Inoue T;Fujimoto T;Kameda T;Awai-Kasaoka N;Ohtsu N;Kimoto K;Tanihara H
青光眼是一种与年龄相关的视网膜神经节细胞退行性疾病，小梁网细胞外基质的适当更新在其病理过程中具有重要意义。在此，我们报道了Rho相关蛋白(ROCK)和p38蛋白激酶在转化生长因子-β-2诱导的人眼小梁细胞I型胶原生成中的作用。转化生长因子-β-2增加RhoA活性、肌动蛋白聚合和肌球蛋白轻链2磷酸化。这些作用可被Y-27632显著抑制，但不能被SB203580所抑制。转化生长因子-COL1A2还可增加β的启动子活性、基因合成和蛋白表达。SB203580可显著抑制上述作用，而Y-27632对其无明显抑制作用。此外，Y-27632对转化生长因子β2诱导的启动子激活、Smad2/3的磷酸化或核转位没有明显的抑制作用，而SB203580则部分抑制了这些过程。总的来说，转化生长因子-Smad2诱导的人眼小梁细胞1型胶原的产生被p38抑制，并伴随着Smad2/3的部分失活。
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.
登录
查看更多内容
影响因子：
--
作者：
ARMALY, MF
通讯作者：
ARMALY, MF
影响因子：
2.7
作者：
Mihira, Hajime;Suzuki, Hiroshi I.;Watabe, Tetsuro
通讯作者：
Watabe, Tetsuro
DOI：
10.1007/s004170000241
发表时间：
2001-02-01
影响因子：
2.7
作者：
Inatani, M;Tanihara, H;Honda, Y
通讯作者：
Honda, Y
影响因子：
3.4
作者：
Junglas, Benjamin;Yu, Alice H. L.;Fuchshofer, Rudolf
通讯作者：
Fuchshofer, Rudolf
影响因子：
4.1
作者：
Kopczynski, Casey;Novack, Gary D.;van Haarlem, Thomas
通讯作者：
van Haarlem, Thomas