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JNK inhibitor SP600125 alleviates TGF-β2-induced epithelial-mesenchymal transition in RPE cell via TGF-βR2/Smad2/3

Hui-Hui Zhang1,2,3, Yu-Sheng Zhu1,2,3, Jing-Yu Guo1,2,3

  • 1Department of Life Sciences and Medicine, Northwest University, Xi'an 710069, Shaanxi Province, China.

International Journal of Ophthalmology
|May 29, 2026
PubMed
Abstract

Insights

A JNK inhibitor, SP600125, effectively suppressed transforming growth factor-beta 2 (TGF-β2)-induced epithelial-mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells. This intervention reduced cell viability, migration, and proliferation by targeting key signaling pathways.

Area of Science:

  • Ophthalmology
  • Cell Biology
  • Molecular Biology

Background:

  • Epithelial-mesenchymal transition (EMT) is a critical cellular process implicated in various ocular diseases.
  • Retinal pigment epithelial (RPE) cells undergo EMT in response to stimuli like transforming growth factor-beta 2 (TGF-β2).
  • Understanding the molecular mechanisms driving TGF-β2-induced EMT in RPE cells is crucial for developing therapeutic strategies.

Purpose of the Study:

  • To investigate the inhibitory effect of SP600125, a c-Jun N-terminal kinases (JNK) inhibitor, on TGF-β2-induced EMT in human RPE cells.
  • To elucidate the underlying signaling pathways modulated by SP600125 in this context.

Main Methods:

  • Human RPE cells (ARPE-19) were treated with TGF-β2 and the JNK inhibitor SP600125 in vitro.
  • Cellular viability, migration, and proliferation were assessed using CCK-8, wound scratch, and BrdU assays.
  • Protein expression and phosphorylation levels of key molecules including TGF-βR2, Smad2/3, JNK, c-Jun, α-SMA, N-cadherin, and vimentin were analyzed via immunoblotting and immunofluorescence.

Main Results:

  • TGF-β2 significantly increased RPE cell viability, migration, and proliferation, alongside inducing EMT markers (α-SMA, N-cadherin, vimentin).
  • TGF-β2 also promoted the phosphorylation of TGF-βR2, Smad2/3, JNK, and c-Jun.
  • SP600125 treatment effectively counteracted these TGF-β2-induced effects, inhibiting cellular proliferation, migration, EMT marker expression, and the phosphorylation of critical signaling proteins.

Conclusions:

  • SP600125 demonstrates a potent inhibitory effect on TGF-β2-induced EMT in RPE cells.
  • The JNK inhibitor suppresses TGF-β2-induced increases in cell viability, migration, and proliferation.
  • These suppressive effects are mediated through the modulation of the TGF-βR2/Smad2/3 and JNK/c-Jun signaling pathways.
Keywords:
SP600125c-Jun N-terminal kinasesepithelial-mesenchymal transitionretinal pigment epithelial celltransforming growth factor-beta 2

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