Deregulation of AP-1 proteins in collagen gel-induced epithelial cell apoptosis mediated by low substratum rigidity

Yao Hsien Wang, Wen Tai Chiu, Yang Kao Wang, Ching Chou Wu, Tsu Ling Chen, Chiao Feng Teng, Wen Tsan Chang, Hsien Chang Chang, Ming Jer Tang

研究成果: Article

23 引文 斯高帕斯(Scopus)


In this study, we established that collagen gel, but not collagen gel coating, induced apoptosis exclusively in epithelial cell lines, which indicated that low substratum rigidity might trigger cell apoptosis. To confirm this, we used collagen gels with different rigidities due to cross-linking or physical disruption of collagen fibrils caused by sonication. We found that collagen gel-induced apoptosis was inversely correlated with substratum rigidity. Low substratum rigidity collagen gel-induced apoptosis was neither prevented by Bcl-2 overexpression nor preceded by mitochondrial release of cytochrome c. This suggested that the mitochondrial pathway was not involved in low substratum rigidity-induced apoptosis. Low substratum rigidity activated c-Jun N-terminal kinase (JNK) within 4 h, but it also rapidly down-regulated c-Jun within 1 h and triggered persistent aberrant expression of c-Fos for at least 24 h. Either reduced c-Jun expression or c-Fos overexpression induced apoptosis in several epithelial cells. Inhibiting low substratum rigidity-induced JNK activation prevented aberrant c-Fos expression but only partially blocked low substratum rigidity-induced apoptosis. Taking these results together, we conclude that low substratum rigidity collagen gel induced apoptosis in epithelial cells and that deregulated AP-1 proteins mediated that apoptosis, at least in part.

頁(從 - 到)752-763
期刊Journal of Biological Chemistry
出版狀態Published - 2007 一月 5


All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology