JNK1/2 siRNA inhibits transforming-growth factor-beta1-induced connective tissue growth factor expression and

Yuan Chang1, Xin-Yi Wu

  • 1Department of Ophthalmology, Qilu Hospital of Shandong University, No. 107, Wenhua Road (West), Lixia District, 250012 Jinan, Shandong, China.

Insights

Transforming-growth factor-beta1 (TGF-beta1) induces connective tissue growth factor (CTGF) in corneal fibrosis. This study reveals CTGF is critical, acting via the JNK signaling pathway in human corneal fibroblasts.

Area of Science:

  • Ophthalmology
  • Cell Biology
  • Molecular Biology

Background:

  • Transforming-growth factor-beta1 (TGF-beta1) is implicated in fibrosis by upregulating connective tissue growth factor (CTGF).
  • The specific signaling pathways involved in TGF-beta1-induced fibrosis in the cornea remain largely uncharacterized.

Purpose of the Study:

  • To investigate the role of CTGF in TGF-beta1-induced fibrosis in human corneal fibroblasts.
  • To elucidate the molecular mechanism, specifically the involvement of the JNK signaling pathway, in TGF-beta1-mediated fibrosis.

Main Methods:

  • Real-time RT-PCR and Western blot analysis were employed to assess CTGF expression.
  • Telomerase-immortalized human cornea stroma fibroblast cells (THSFs) were utilized.
  • JNK pathway activation was detected, and JNK1/2 siRNA was used to block the pathway.

Main Results:

  • TGF-beta1 and CTGF both promoted THSF cell proliferation, which was inhibited by anti-CTGF antibody.
  • TGF-beta1 stimulation led to CTGF upregulation and THSF cell proliferation.
  • Blocking the JNK pathway with JNK1/2 siRNA significantly reduced TGF-beta1-induced CTGF expression.

Conclusions:

  • Connective tissue growth factor (CTGF) plays a critical role in the corneal fibrosis process.
  • TGF-beta1 induces corneal fibrosis partly through the upregulation and activation of the JNK signaling pathway.
  • Targeting the CTGF-JNK axis may offer therapeutic strategies for corneal fibrosis.

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