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Binding with HSP90β, cimifugin ameliorates fibrotic cataracts in vitro andin vivo by inhibiting TGFβ signaling pathways

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机构： [1]Beijing Tongren Hospital, Beijing, 100730, China [2]Capital Medical University, Beijing, 100730, China [3]Beijing Tongren Eye Center, Beijing, 100730, China [4]Beijing Ophthalmology&Visual Sciences Key Lab, Beijing, 100730, China [5]The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Key Laboratory of Molecular Drug Research, Nan kai University, Tianjin, 300071, China

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关键词： Cimifugin HSP90β Epithelial-mesenchymal transition TGFβRII

摘要：

Fibrotic cataracts, the most frequent complications after phacoemulsification, cannot be cured by drugs in clinic. The primary mechanism underlying the disease is the epithelial-mesenchymal transition (EMT). Cimifugin is a natural monomer component of traditional Chinese medicines. Previous researches have demonstrated the effect of cimifugin inhibiting EMT in the lung. The purpose of this work is to evaluate the impact of cimifugin on EMT in the lens and elucidate its precise mechanism. The pathogenesis of fibrotic cataracts was simulated using TGFβ2-induced cell model of EMT and the injury-induced anterior subcapsular cataract animal model. Through H&E staining and immunofluorescence of mice eyeballs, we discovered that cimifugin can inhibit the expansion of fibrotic lesions in vivo. Furthermore, at mRNA and protein levels, we confirmed that cimifugin can allay EMT of lens epithelial cells (LECs) in vitro and in vivo. Additionally, the inhibition of cimifugin on the activation of TGFβ-related signaling pathways was certified by immunoblot. HSP90β, the target of cimifugin, was predicted by network pharmacology and verified by drug affinity responsive target stability, the cellular thermal shift assay, and microscale thermophoresis. Moreover, co-immunoprecipitation revealed the interaction between HSP90β and TGFβ receptor (TGFβR) II. Together, our findings showed that by weakening the binding of HSP90β and TGFβRII, cimifugin suppressed the TGFβ signaling pathways to alleviate fibrotic cataracts. Cimifugin is a promising medication for the treatment of fibrotic cataracts.Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.

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出版当年[2023]版：

大类 | 2 区医学

小类 | 2 区眼科学

最新[2025]版：

大类 | 3 区医学

小类 | 2 区眼科学

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出版当年[2022]版：

Q2 OPHTHALMOLOGY

最新[2024]版：

Q2 OPHTHALMOLOGY

影响因子： 2.7 最新[2024版] 3.3 最新五年平均 3.4 出版当年[2022版] 3.6 出版当年五年平均 3.77 出版前一年[2021版] 3 出版后一年[2023版]

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第一作者机构： [1]Beijing Tongren Hospital, Beijing, 100730, China [2]Capital Medical University, Beijing, 100730, China

通讯作者：

通讯机构： [1]Beijing Tongren Hospital, Beijing, 100730, China [2]Capital Medical University, Beijing, 100730, China [3]Beijing Tongren Eye Center, Beijing, 100730, China [4]Beijing Ophthalmology&Visual Sciences Key Lab, Beijing, 100730, China

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