Characterization of TGF-β by Induced Oxidative Stress in Human Trabecular Meshwork Cells

Chen, Hsin-Yi and Chou, Hsiu-Chuan and Ho, Yi-Jung and Chang, Shing-Jyh and Liao, En-Chi and Wei, Yu-Shan and Lin, Meng-Wei and Wang, Yi-Shiuan and Chien, Yu-An and Yu, Xin-Ru and Kung, Hsiang-Yu and Yang, Chu-Chun and Chen, Jia-Yu and Chan, Hong-Lin and Ko, Mei-Lan (2021) Characterization of TGF-β by Induced Oxidative Stress in Human Trabecular Meshwork Cells. Antioxidants, 10 (1). p. 107. ISSN 2076-3921

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Abstract

Oxidative stress generated by reactive oxygen species (ROS) plays a critical role in the pathomechanism of glaucoma, which is a multifactorial blinding disease that may cause irreversible damage within human trabecular meshwork cells (HTMCs). It is known that the transforming growth factor-β (TGF-β) signaling pathway is an important component of oxidative stress-induced damage related to extracellular matrix (ECM) fibrosis and activates cell antioxidative mechanisms. To elucidate the dual potential roles and regulatory mechanisms of TGF-β in effects on HTMCs, we established an in vitro oxidative model using hydrogen peroxide (H2O2) and further focused on TGF-β-related oxidative stress pathways and the related signal transduction. Via a series of cell functional qualitative analyses to detect related protein level alterations and cell fibrosis status, we illustrated the role of TGF-β1 and TGF-β2 in oxidative stress-induced injury by shTGF-β1 and shTGF-β2 knockdown or added recombinant human TGF-β1 protein (rhTGF-β1). The results of protein level showed that p38 MAPK, TGF-β, and its related SMAD family were activated after H2O2 stimulation. Cell functional assays showed that HTMCs with H2O2 exposure duration had a more irregular actin architecture compared to normal TM cells. Data with rhTGF-β1 (1 ng/mL) pretreatment reduced the cell apoptosis rate and amount of reactive oxygen species (ROS), while it also enhanced survival. Furthermore, TGF-β1 and TGF-β2 in terms of antioxidant signaling were related to the activation of collagen I and laminin, which are fibrosis-response proteins. Succinctly, our study demonstrated that low concentrations of TGF-β1 (1 ng/mL) preserves HTMCs from free radical-mediated injury by p-p38 MAPK level and p-AKT signaling balance, presenting a signaling transduction mechanism of TGF-β1 in HTMC oxidative stress-related therapies.

Item Type: Article
Subjects: Open STM Article > Agricultural and Food Science
Depositing User: Unnamed user with email support@openstmarticle.com
Date Deposited: 05 Jul 2023 04:25
Last Modified: 05 Jun 2024 10:16
URI: http://asian.openbookpublished.com/id/eprint/1234

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