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Knockout of TGF-β receptor II by CRISPR/Cas9 delays mesenchymal transition of Lens epithelium and posterior capsule opacification

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机构: [1]Beijing Tongren Hospital, Capital Medical University, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing 100730, China [2]Department of Ophthalmology, Beijing Shijitan Hospital of Capital Medical University, Beijing 100038, China [3]Beijing Tongren Hospital, Beijing Institute of Ophthalmology, Capital Medical University, Beijing Key Laboratory of Ophthalmology & Visual Sciences, Beijing 100730, China
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关键词: CRISPR-Cas9 Epithelial- mesenchymal transition lens epithelial cells TGF-βRII PCO

摘要:
Posterior capsule opacification (PCO) is the most common postoperative complication of cataract surgery. Transforming growth factor-β (TGF-β) is related to epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) that is proven to induce PCO formation in clinical and experimental studies. In this study, CRISPR sequences targeting exon of TGF-βRII were knocked out with lentiviral transfection in LECs. Rabbits' PCO model was established and recombinant adeno-associated virus (AAV) for transferring the gRNA of TGF βRII were intravitreally injected. SgRNA inhibited TGF-βRII expression and human LECs proliferation. In TGF-βRII knockout group, LECs motility and migration were suppressed, N-cadherin and vimentin expressions were significantly decreased, whereas E-cadherin was increased. The animal model showed that TGF-βRII knockout in vivo was effective in suppressing PCO. The current study suggested that the CRISPR/Cas9 endonuclease system could suppress TGF-βRII secretion, which participates in the EMT procedure of LECs in vitro and PCO in vivo. These findings might provide a new gene-editing approach and insight into a novel therapeutic strategy for PCO.Copyright © 2024 Elsevier B.V. All rights reserved.

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出版当年[2023]版:
大类 | 1 区 化学
小类 | 1 区 应用化学 1 区 高分子科学 2 区 生化与分子生物学
最新[2025]版:
大类 | 2 区 生物学
小类 | 2 区 生化与分子生物学 2 区 应用化学 2 区 高分子科学
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出版当年[2022]版:
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Q1 CHEMISTRY, APPLIED Q1 POLYMER SCIENCE
最新[2023]版:
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Q1 CHEMISTRY, APPLIED Q1 POLYMER SCIENCE

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第一作者机构: [1]Beijing Tongren Hospital, Capital Medical University, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing 100730, China
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