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JAM-C prevents ocular fibrosis by suppressing the TAZ/KLF6 pathway

Min Chen1, Wanhong Li1, Yuxiang Du2

  • 1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University and Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, China.

Journal of Advanced Research
|May 21, 2025
PubMed
Abstract

Insights

Junctional adhesion molecule C (JAM-C) prevents ocular fibrosis by inhibiting the TAZ/KLF6 pathway. Augmenting JAM-C shows therapeutic potential for treating fibrotic eye diseases and preventing blindness.

Area of Science:

  • Ophthalmology
  • Cell Biology
  • Molecular Medicine

Background:

  • Ocular fibrosis leads to irreversible vision loss, with no current effective drug treatments.
  • Understanding the molecular mechanisms of ocular fibrosis is crucial for developing new therapies.

Purpose of the Study:

  • To investigate the role of junctional adhesion molecule C (JAM-C) in the development of ocular fibrosis.
  • To explore JAM-C's potential as a therapeutic target for fibrotic eye diseases.

Main Methods:

  • Quantified JAM-C levels in patient vitreous humor using ELISA.
  • Utilized JAM-C knockout mice and induced ocular fibrosis models.
  • Assessed epithelial-mesenchymal transition (EMT), proliferation, and migration in RPE cells following JAM-C knockdown.
  • Employed RNA sequencing, co-immunoprecipitation, ChIP-qPCR, and luciferase assays to elucidate mechanisms.
  • Evaluated therapeutic potential using adeno-associated virus (AAV)-mediated JAM-C delivery in mouse models.

Main Results:

  • Reduced JAM-C expression observed in patients with ocular fibrosis.
  • JAM-C deficiency exacerbated fibrosis in mice; JAM-C knockdown induced EMT in RPE cells.
  • JAM-C inhibits ocular fibrosis by suppressing TAZ nuclear localization and its interaction with KLF6, a key EMT inducer.
  • AAV-mediated JAM-C augmentation effectively alleviated ocular fibrosis in vivo.

Conclusions:

  • JAM-C plays a protective role against ocular fibrosis by inhibiting the TAZ/KLF6 pathway.
  • JAM-C represents a novel therapeutic target for treating ocular fibrotic diseases.
  • These findings open new avenues for therapeutic strategies against irreversible blindness caused by fibrosis.
Keywords:
Epithelial-mesenchymal transitionFibrosisJAM-CKLF6TAZ

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