Low-dose paclitaxel modulates the cross talk between the JNK and Smad signaling in primary biliary fibroblasts

Jiamei Lu1, Liang Yu2, Jianhua Shi2

  • 1The Second Affiliated Hospital of Xi'an Jiaotong University, Department of Nephrology - Xi'an, China.

Revista Da Associacao Medica Brasileira (1992)
|March 3, 2022
PubMed
Abstract

Insights

Transforming growth factor beta 1 activates JNK/Smad2L, leading to benign bile duct stricture via collagen overexpression. Low-dose paclitaxel may prevent this by inhibiting JNK/Smad2L phosphorylation.

Area of Science:

  • Gastroenterology and Hepatology
  • Molecular Biology
  • Oncology

Background:

  • Benign bile duct stricture (BBDS) pathogenesis involves complex molecular signaling.
  • Fibroblast activation and extracellular matrix deposition are key features of BBDS.

Purpose of the Study:

  • To elucidate the molecular mechanisms of BBDS.
  • To investigate low-dose paclitaxel as a potential therapeutic agent for BBDS prevention.

Main Methods:

  • Primary fibroblasts were stimulated with transforming growth factor beta 1 (TGF-β1).
  • Expression of collagen type I (COL1) and connective tissue growth factor (CTGF) was measured.
  • Western blot analysis detected phosphorylation of JNK and Smad2L.
  • Effects of low-dose paclitaxel on TGF-β1-induced changes were assessed.

Main Results:

  • TGF-β1 stimulated COL1 and CTGF secretion and JNK phosphorylation in biliary fibroblasts.
  • JNK inhibition or Smad2 knockdown attenuated TGF-β1-induced COL1 and CTGF secretion.
  • Low-dose paclitaxel inhibited TGF-β1-induced COL1 expression and potentially collagen secretion.

Conclusions:

  • TGF-β1-induced JNK/Smad2L activation drives BBDS through COL1 and CTGF overexpression.
  • Low-dose paclitaxel demonstrates potential in inhibiting the JNK/Smad2L pathway, offering a preventive strategy for BBDS.

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