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Department of Physiology, National Cheng Kung University Medical College, Tainan, Taiwan, Republic of China
In this study, we attempted to investigate the response of
polarized cells to inappropriate interaction with the extracellular matrix. Cell lines of epithelial [Madin-Darby canine kidney
(MDCK) and LLC-PK1],
endothelial [bovine aortic endothelial cells (BAEC)], and
mesenchymal (ESK-4 and NIH/3T3) origins were employed. With collagen
gel overlay, MDCK cells underwent membrane remodeling and gradually
developed lumen formation within 24 h. Apoptosis could also be observed
following cell remodeling. The ratio of apoptosis was enhanced from
12.1 ± 2.4% within 24 h to 58.4 ± 9.8% at
day 3, and finally the monolayer was
disintegrated. Collagen gel overlay-induced apoptosis was not a result
of physical stress, since agarose gel overlay did not induce any
morphological alterations. All epithelial and endothelial cells
examined developed apoptosis in response to collagen overlay. In
contrast, collagen overlay did not affect growth of fibroblasts at all,
although their growth under agarose gel was slightly hindered due to
physical stress. Collagen overlay-induced apoptosis seems to be a
unique phenomenon for polarized cells and thus is defined as
"disoriented cell death." Furthermore,
anti-
2-integrin antibody could
abolish collagen overlay-induced morphological changes and apoptosis in
MDCK cells, indicating that signals through
2-integrin on the apical
membrane are required for disoriented cell death. Finally, Bcl-2
overexpression prolonged survival of MDCK cells in response to collagen
overlay, but these cells eventually developed apoptosis due to
downregulation of Bcl-2 protein. These findings indicate that
inappropriate cell-matrix interaction results in apoptosis, which may
account for cell death mechanisms during developmental processes or
under pathological conditions.
integrin; Bcl-2; membrane remodel; epithelium
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