|Elevated pressure downregulates ZO-1 expression and disrupts cytoskeleton and focal adhesion in human trabecular meshwork cells|
|Yang, Xuejiao1; Liu, Bingqian1; Bai, Yujing1,2; Chen, Min1,3; Li, Yiqing1; Chen, Mengfei1; Wei, Yantao1; Ge, Jian1; Zhuo, Yehong1|
|WOS标题词||Science & Technology|
|类目[WOS]||Biochemistry & Molecular Biology ; Ophthalmology|
|研究领域[WOS]||Biochemistry & Molecular Biology ; Ophthalmology|
|关键词[WOS]||RETINAL GANGLION-CELLS ; OPEN-ANGLE GLAUCOMA ; TIGHT JUNCTIONS ; PROTEIN ZO-1 ; APOPTOSIS ; ORGANIZATION ; VINCULIN ; DEATH|
Purpose: To investigate the effect of elevated hydrostatic pressure on the expression and distribution of zonula occludens-1 (ZO-1), and its effect on cytoskeleton and focal adhesion in immortal human trabecular meshwork cells (iHTM) and glaucomatous human trabecular meshwork cells (GTM(3)).
Methods: iHTM and GTM(3) were exposed to 60 mmHg hydrostatic pressure for 6, 12, and 24 h. As a control, the cells were incubated simultaneously in a conventional incubator. Morphology changes were observed with an inverted microscope. The expression of ZO-1was examined with western blot, and the distribution of ZO-1 was assessed by immunofluorescence. Actin cytoskeleton and focal adhesion (vinculin) were also assessed by immunofluorescence. Data were analyzed with commercial data analysis software and a p<0.05 was considered to be statistically significant.
Results: There was no evident morphology change after 24 h culture in 60 mmHg pressure in iHTM and GTM(3). However, in both iHTM and GTM(3), elevated pressure attenuated the expression of ZO-1 at 12 h and 24 h, detected by western blot. Meanwhile, high pressure disrupted the organization of ZO-1, actin cytoskeleton, and vinculin, assessed by immunofluorescence. When comparing iHTM with GTM(3), the distribution of ZO-1 and vinculin in GTM(3) was not as regular as that in iHTM. After exposuring in elevated pressure, the changes in GTM(3) were more obvious than that in iHTM.
Conclusions: Sustained pressure elevation may directly damage trabecular meshwork cells by injuring ZO-1, cytoskeleton, and foal adhesions. And GTM(3) was more susceptible to damage than iHTM. We suggest that elevated pressure seems to be not only the results of damaged TM, but also an important factor for the injury of TM cells, stop or reverse the process may help developing new target for the treatment of primary open angle glaucoma (POAG).
|项目编号||30872832 ; 81000376 ; 10251008901000028 ; 9451008901001999|
|资助机构||Guangdong Province Universities and Colleges ; National Natural Science Foundation of China ; Natural Science Foundation of Guangdong Province|
|作者单位||1.Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China|
2.Peking Univ, Peoples Hosp, Dept Ophthalmol, Key Lab Vis Loss & Restorat,Minist Educ, Beijing 100871, Peoples R China
3.Zhejiang Univ, Affiliated Hosp 2, Dept Ophthalmol, Hangzhou, Zhejiang, Peoples R China
|Yang, Xuejiao,Liu, Bingqian,Bai, Yujing,et al. Elevated pressure downregulates ZO-1 expression and disrupts cytoskeleton and focal adhesion in human trabecular meshwork cells[J]. MOLECULAR VISION,2011,17(320-21):2978-2984.|
|APA||Yang, Xuejiao.,Liu, Bingqian.,Bai, Yujing.,Chen, Min.,Li, Yiqing.,...&Zhuo, Yehong.(2011).Elevated pressure downregulates ZO-1 expression and disrupts cytoskeleton and focal adhesion in human trabecular meshwork cells.MOLECULAR VISION,17(320-21),2978-2984.|
|MLA||Yang, Xuejiao,et al."Elevated pressure downregulates ZO-1 expression and disrupts cytoskeleton and focal adhesion in human trabecular meshwork cells".MOLECULAR VISION 17.320-21(2011):2978-2984.|