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Updated: Oct 1, 2025

Long-term Live-cell Imaging to Assess Cell Fate in Response to Paclitaxel
Published on: May 14, 2018
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.
Objective:
The objective of this study was to explore the molecular mechanism underlying the occurrence of benign bile duct stricture and the target of low-dose paclitaxel in the prevention of benign bile duct stricture.
Methods:
Under the stimulation of transforming growth factor beta 1, the expression of collagen type I and connective tissue growth factor were detected on isolated primary fibroblasts. The phosphorylation levels of JNK and Smad2L were detected using Western blot. The effect of low-dose paclitaxel on the transforming growth factor beta 1-induced inhibition of type I collagen and connective tissue growth factor expression and JNK and Smad2L phosphorylation was also observed.
Results:
Transforming growth factor beta 1 induced the secretion of type I collagen and connective tissue growth factor as well as JNK phosphorylation in biliary fibroblasts. The JNK inhibitor or siRNA-Smad2 inhibited the transforming growth factor beta 1-induced secretion of type I collagen and connective tissue growth factor. Low-dose paclitaxel inhibited the expression of type I collagen induced by transforming growth factor beta 1 and may inhibit the secretion of collagen in biliary fibroblasts.
Conclusion:
The activation of JNK/Smad2L induced by transforming growth factor beta 1 is involved in the occurrence of benign bile duct stricture that is mediated by the overexpression of type I collagen and connective tissue growth factor, and low-dose paclitaxel may inhibit the phosphorylation of JNK/Smad2L.
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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