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

  • Int J Ophthalmol. 2025 May 18;18(5):779-791. doi: 10.18240/ijo.2025.05.03.
Ke-Ke Zhang  1 ,  Meng Li  2 ,  Yan-Hong Liao  2 ,  Xiao-Tian Liu  2 ,  Yong-Bo Bao  3 ,  Yan Gong  2
Affiliations
  • 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.
PMID: 40385123 DOI: 10.18240/ijo.2025.05.03
Abstract

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 1 µmol/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-β independently 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.

Keywords
co-immunoprecipitation; epithelial-mesenchymal transition; molecular docking; nintedanib; pterygium.
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