Cytoskeletal signaling by way of α-actinin-1 mediates ERK1/2 activation by repetitive deformation in human Caco2 intestinal epithelial cells

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• 作者：David H. Craig ; Jianhu Zhang ; Marc D. Basson
• 关键词：Intestinal epithelial cell ; Mechanotransduction ; Proliferation ; Strain
• 刊名：The American Journal of Surgery
• 出版年：2007
• 期刊代码：9_00029610
• 类别：med
• 出版时间：November 2007
• 卷：194
• 期：5
• 页码：618-622
• 文件大小：404 K

摘要

Repetitive deformation stimulates proliferation in human Caco2 intestinal epithelial cells by way of an ERK1/2-dependent pathway. We examined the effects of cytoskeletal perturbation on deformation-induced signaling in Caco2 cells.

Methods

The Caco2 cell cytoskeleton was disrupted with either cytochalasin D, phalloidin, colchicine, or paclitaxel. Levels of α-actinin-1 and -4 and paxillin were reduced by specific small interfering RNA. Cells on collagen I–precoated membranes were subjected to 10%repetitive deformation at 10 cycles/min. After 1 hour, cells were lysed for Western blot analysis.

Results

Strain-activated ERK1/2, focal adhesion kinase, and Src phosphorylation in dimethyl sulfoxide- and/or nontargeting small interfering RNA-treated control cell populations. Cytochalasin D and paclitaxel, but not phalloidin and colchicine, blocked ERK1/2 phosphorylation. A decrease in α-actinin-1, but not in α-actinin-4 or paxillin, inhibited ERK1/2 and focal adhesion kinase phosphorylation, whereas Src activation appears to be independent of these effects.

Conclusions

The intestinal epithelial cell cytoskeleton may transduce mechanical signals by way of α-actinin-1 into the focal adhesion complex, culminating in ERK1/2 activation and proliferation.