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

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.

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.

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.

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.