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Abstract #81272 Published in IGR 20-3
1α,25-dihydroxyvitamin D3 attenuates oxidative stress-induced damage in human trabecular meshwork cells by inhibiting TGFβ-SMAD3-VDR pathway
Lv Y; Han X; Yao Q; Zhang K; Zheng L; Hong W; Xing XBiochemical and Biophysical Research Communications 2019; 516: 75-81
Evidence indicates that 1α, 25-dihydroxy vitamin D3 (1, 25-(OH)D) markedly reduces intraocular pressure (IOP) in nonhuman primates, while the biochemical mechanisms are unclear. To investigate the influence of oxidative stress on human trabecular meshwork cells (HTMCs) and the effect and regulatory mechanism of 1, 25-(OH)D in HTMCs under oxidative stress, we established an oxidative stress model in HTMCs using hydrogen peroxide (HO) and showed that 1, 25-(OH)D could inhibit oxidative stress-induced apoptosis and reduce extracellular matrix (ECM) composition of HTMCs. Moreover, 1, 25-(OH)D could attenuate HO-induced inflammation in HTMCs. Mechanistically, our findings revealed that HO-induced damage was mediated by the transforming growth factor-β (TGF-β)-SMAD3 pathway in HTMCs, and 1, 25-(OH)D could protect HTMCs against oxidative stress through vitamin D receptor (VDR), which antagonises the effects of SMAD3. Overall, these findings define a mechanism by which 1, 25-(OH)D reduces ECM accumulation and suppresses the TGF-β-SMAD3-VDR pathway in HTMCs, thus protecting the cells from oxidative stress, suggesting 1, 25-(OH)D might be a potential therapeutic for glaucoma.
Tianjin Medical University Eye Hospital, Tianjin Medical University Eye Institute, School of Optometry & Ophthalmology, Tianjin, China. Electronic address: Lvyingjuan@tmu.edu.cn.
Full articleClassification:
3.8 Pharmacology (Part of: 3 Laboratory methods)
3.6 Cellular biology (Part of: 3 Laboratory methods)
2.5.1 Trabecular meshwork (Part of: 2 Anatomical structures in glaucoma > 2.5 Meshwork)
