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Experimental eye research

Experimental eye research

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

Published:17 October 2024 DOI: 10.1016/j.exer.2024.110127 PMID: 39424221
Xuefei Ding , Zhaochuan Liu , Hailong Li , Peilin Yue , Yuxuan Jia , Enjie Li , Ningxin Lv , Ting Chen , Rui Fang , Honggang Zhou , Xudong Song

Abstract

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.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Cimifugin 37921-38-3 C16H18O6 223 suppliers $16.00-$1060.00
Cimifugin 37921-38-3 C16H18O6 223 suppliers $16.00-$1060.00
Cimifugin 37921-38-3 C16H18O6 223 suppliers $16.00-$1060.00
Cimifugin 37921-38-3 C16H18O6 223 suppliers $16.00-$1060.00

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