Tissue remodeling during tumor necrosis factor-induced apoptosis in
llc-pk1 renal epithelial cells.
Soler, Alejandro Peralta, James M. Mullin, Karen A. Knudsen, and
Colleen W. Marano.
The Lankenau Medical Research Center, 100 Lancaster Avenue,
Wynnewood, PA 19096
APStracts 2:0198F, 1995.
The cytokine tumor necrosis factor-[alpha] (TNF) increases the
frequency of apoptosis in confluent renal epithelial LLC-PK1 cells,
an effect that can be blocked by an anti-TNFR1 monoclonal antibody.
However, there were no visible "holes" in the cell sheet as a
result of TNF-induced apoptosis. Instead, a striking tissue
remodeling occurred in response to the TNF-induced apoptosis.
Apoptotic cells became surrounded and engulfed by repositioned
neighboring cells distributed in a distinct "rosette"
pattern. The cadherin/catenin cell-cell adhesion molecules, the tight
junction-associated protein ZO-1 and actin accumulated at the sites
of contact between apoptotic and neighboring cells. Pretreatment with
cytochalasin B prevented the accumulation of cadherins/catenins and
ZO-1 at the sites of apoptosis and resulted in microscopic holes in
the TNF-treated cell sheet. Our results indicate that a renal
epithelium can accommodate an increased frequency of apoptosis and
still maintain its integrity by mechanisms of tissue remodeling
involving the cadherin/catenin adhesion molecules, tight junctional
proteins and actin filaments.
Received 6 July 1995; accepted in final form 3 November 1995.
APS Manuscript Number F214-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 November 95