HES1 promotes extracellular matrix protein expression and inhibits proliferation and migration in human trabecular meshwork cells under oxidative stress
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Linqi Xu1,2,*, Yan Zhang1,*, Ruru Guo1,*, Wencui Shen1,2, Yan Qi1,2, Qingsong Wang2, Zhenglong Guo2, Chen Qi1, Haifang Yin2, Jiantao Wang1
1Tianjin Medical University Eye Hospital, Tianjin Medical University Eye Institute, College of Optometry and Ophthalmology, Tianjin Medical University, Tianjin 300384, China
2Tianjin Research Center of Basic Medical Sciences and Department of Cell Biology, Tianjin Medical University, Tianjin 300070, China
*These authors have contributed equally to this work
Jiantao Wang, email: firstname.lastname@example.org
Haifang Yin, email: email@example.com
Keywords: oxidative stress, glaucoma, trabecular meshwork, extracellular matrix, HES1
Received: November 22, 2016 Accepted: February 07, 2017 Published: February 23, 2017
Glaucoma is the leading cause of irreversible blindness. The most prevalent form of glaucoma is primary open-angle glaucoma (POAG). Oxidative stress is one of the major pathogenic factors of the POAG, and can elicit molecular and functional changes in trabecular meshwork cells, causing increased aqueous humor outflow resistance and elevated intraocular pressure. However, the regulatory mechanisms underlying oxidative stress-induced cell phenotypic changes remain elusive. Herein, we exposed primary human trabecular meshwork cells to the oxidative stress induced by 300 μM H2O2 for 2 h, and found significantly up-regulated expression of extracellular matrix proteins and a transcription factor, hairy and enhancer of split-1 (HES1). The cell functions, including migration and proliferation, were impaired by the oxidative stress. Furthermore, HES1 shRNA abrogated the extracellular matrix protein up-regulation and rescued the functional defects caused by the oxidative stress; conversely, HES1 overexpression resulted in the molecular and functional changes similar to those induced by H2O2. These results suggest that HES1 promotes extracellular matrix protein expression and inhibits proliferative and migratory functions in the trabecular meshwork cells under oxidative stress, thereby providing a novel pathogenic mechanism underlying and a potential therapeutic target to the POAG.
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