Academic Journal
Elevated Angiotensin-II Levels Contribute to the Pathogenesis of Open-Angle Glaucoma Via Inducing the Expression of Fibrosis-Related Genes in Trabecular Meshwork Cells Through a ROS/NOX4/SMAD3 Axis
| العنوان: | Elevated Angiotensin-II Levels Contribute to the Pathogenesis of Open-Angle Glaucoma Via Inducing the Expression of Fibrosis-Related Genes in Trabecular Meshwork Cells Through a ROS/NOX4/SMAD3 Axis |
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| المؤلفون: | Li, Haijun, Cui, Huiling, Ren, Jing, Wang, Di, Zhao, Rumeng, Zhu, Shichao, Liu, Siqing, Liu, Xiaohui, Tian, Shuai, Zhang, Yuanyuan, Zhao, Panpan, Li, Peng, Thorne, Rick F., Duan, Shichao |
| المساهمون: | Henan Medical Science and technology research plan, National Natural Science Foundation of China |
| المصدر: | Cell Transplantation ; volume 32 ; ISSN 0963-6897 1555-3892 |
| بيانات النشر: | SAGE Publications |
| سنة النشر: | 2023 |
| الوصف: | Glaucoma including primary open-angle glaucoma (POAG) results from elevations in intraocular pressure (IOP). An eye-localized renin-angiotensin system (RAS) has been implicated in IOP regulation, although its mechanism of action and contribution to glaucoma is poorly understood. Here, we detected significant increases in the levels of angiotensin II (ANGII) in aqueous humor samples from POAG patients. Moreover, we determined that the concentrations of ANGII were positively correlated with IOP, suggesting a role for elevated ANGII levels in eye pathogenesis. Functional investigations demonstrated that ANGII induces the expression of fibrosis-related genes of transformed and primary human trabecular meshwork cells (HTMCs) through the transcriptional upregulation of key fibrotic genes. Parallel experiments using a murine periocular conjunctival fornix injection model confirmed that ANGII induces the expression of fibrosis-related genes in trabecular meshwork (TM) cells in vivo along with increasing IOP. ANGII was revealed to function through increasing the levels of reactive oxygen species (ROS) via selectively upregulating NOX4, with NOX4 knockdown or inhibition with GLX351322 alleviating fibrotic changes induced by ANGII. We further show that ANGII activates Smad3, with both GLX351322 and an inhibitor of Smad3 (SIS3) decreasing the phosphorylation of Smad3 and dampening the ANGII-induced increases in fibrotic proteins. Moreover, NOX4 and Smad3 inhibitors also partially rescued the elevated IOP levels induced by ANGII. Our collective results therefore highlight ANGII as a biomarker and treatment target in POAG together with establishing a causal relationship between ANGII and up-regulation of the expression of fibrosis-related genes of TM cells via a NOX4/ROS axis in cooperation with TGFβ/Smad3 signaling. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1177/09636897231162526 |
| الاتاحة: | https://doi.org/10.1177/09636897231162526 https://journals.sagepub.com/doi/pdf/10.1177/09636897231162526 https://journals.sagepub.com/doi/full-xml/10.1177/09636897231162526 |
| Rights: | https://creativecommons.org/licenses/by-nc/4.0/ |
| رقم الانضمام: | edsbas.F86FC352 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1177/09636897231162526 |
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