https://scholars.lib.ntu.edu.tw/handle/123456789/639087
標題: | TGF-β1 signaling protects retinal ganglion cells from oxidative stress via modulation of the HO-1/Nrf2 pathway | 作者: | Chen, Hsin-Yi Ho, Yi-Jung Chou, Hsiu-Chuan Liao, En-Chi Tsai, Yi-Ting Wei, Yu-Shan Lin, Li-Hsun Lin, Meng-Wei Wang, Yi-Shiuan MEI-LAN KO Chan, Hong-Lin |
關鍵字: | HO-1/Nrf2 pathway; Oxidative stress; Retinal ganglion cells; TGF-β1 | 公開日期: | 1-十一月-2020 | 卷: | 331 | 來源出版物: | Chemico-biological interactions | 摘要: | Oxidative stress provides a major contribution to the pathogenesis of glaucoma and may induce retinal ganglion cell (RGC) damage. Transforming growth factor β (TGF-β) has appeared as a neuroprotective protein in various indignities. However, the TGF-β mechanism of protective effects against oxidative stress damage in RGCs still undetermined. In our research, we investigated the regulatory mechanisms and potential effects of TGF-β1 & TGF-β2 in hydrogen peroxide (H2O2)-stimulated oxidative stress of RGCs in vitro. By a series of cell functional qualitative analysis, such as MTT cell viability assay, wound healing ability assay, apoptosis assay, intracellular ROS detection, immunoblot analysis, intracellular GSH content, and high-resolution respirometry, we illustrated the cell state in oxidative stress-induced injury. Results of protein expression showed that TGF-β1 & TGF-β2 was upregulated in RGCs after H2O2 stimulation. Cell functional assays resulted that knockdown of TGF-β1 & TGF-β2 reduced survival rate whereas enhanced apoptosis and accumulation of reactive oxygen species (ROS). Especially TGF-β1 upregulation promoted the protein expression of aldehyde dehydrogenase 3A1 (ALDH3A1) and increased the activity of antioxidant and neuroprotection pathways. Additionally, TGF-β1 & TGF-β2 on antioxidant signaling was related to activation of heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor (Nrf2), which are stress-response proteins. ROS accumulation followed by the accumulation of hypoxia-inducible factor (HIF-1α) caused mitochondrial damage and led to neurodegeneration. In summary, our results demonstrated that TGF-β1 preserves RGCs from free radicals-mediated injury by upregulating the activation of Nrf2 expression and HO-1 signaling balance HIF-1α upregulation, implying a prospective role of TGF-β1 in retinal neuroprotection-related therapies. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/639087 | ISSN: | 00092797 | DOI: | 10.1016/j.cbi.2020.109249 |
顯示於: | 醫學院附設醫院 (臺大醫院) |
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