Nintedanib regulates miR-23b-3p/TGFBR2 axis and competitively binds to TGFBR2 protein, inhibiting EMT process in human pterygium cells  

作　　者：Ke-Ke Zhang Meng Li Yan-Hong Liao Xiao-Tian Liu Yong-Bo Bao Yan Gong 

机构地区：[1]Health Science Center,Ningbo University,Ningbo 315211,Zhejiang Province,China [2]Ningbo Eye Institute,Ningbo Eye Hospital,Wenzhou Medical University,Ningbo 315040,Zhejiang Province,China [3]College of Biological and Environmental Sciences,Zhejiang Wanli University,Ningbo 315100,Zhejiang Province,China

出　　处：《International Journal of Ophthalmology(English edition)》2025年第5期779-791,共13页国际眼科杂志(英文版)

基　　金：Supported by the Ningbo Natural Science Foundation(No.2023J212);Zhejiang Medical and Health Technology Program(No.2023KY1141).

摘　　要：AIM:To investigate the effects of nintedanib on epithelial-mesenchymal transition(EMT)in cells derived from pterygium,aiming to explore its potential as a pharmacological intervention for pterygium treatment.METHODS:Primary human pterygium epithelial cells(hPEC)and human conjunctival epithelial(hCJE)cells were isolated from patients,cultured,and characterized.The impact of nintedanib on transforming growth factor beta(TGF-β)-induced EMT was assessed by examining the expression of EMT markers such as vimentin and E-cadherin.Additionally,the modulation of the miR-23b-3p/transforming growth factor beta receptor 2(TGFBR2)/Smad2 pathway by nintedanib was investigated to elucidate its potential antifibrotic mechanism.RESULTS:The expression of miR-23b-3p gene in hCJE cells was significantly higher than that in hPEC cells.Nintedanib effectively mitigated TGF-β-induced EMT in cells derived from pterygium,as evidenced by the downregulation of vimentin and upregulation of E-cadherin.When the nintedanib concentration exceeded 1μmol/L,it significantly suppressed the proliferation of hPEC cells and significantly inhibited the migration distance of hPEC cells within 48h(P<0.01).The immunoprecipitation experiment showed that nintedanib modulated the TGFBR2 protein’s response to TGF-βindependently of miR-23b-3p.Both nintedanib and transfection with miR-23b-3p mimic significantly inhibited the expression levels of phosphorylated Smad2,snail homolog 1(Drosophila,SNAIL),and SNAI2(also known as SLUG,snail family transcriptional repressor 2)proteins.CONCLUSION:Nintedanib is found to modulate the miR-23b-3p/TGFBR2/Smad2 pathway,suggesting a novel antifibrotic mechanism.These findings collectively highlight nintedanib’s therapeutic potential in managing pterygium,marking a significant step toward non-surgical treatment options.Nintedanib may offer a targeted pharmacological treatment that could complement or reduce the need for surgical interventions.

关 键 词：PTERYGIUM epithelial-mesenchymal transition nintedanib molecular docking CO-IMMUNOPRECIPITATION 

分 类 号：R777.33[医药卫生—眼科]