Tissue remodeling during tumor necrosis factor-induced apoptosis in LLC-PK1 renal epithelial cells.
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.
Peralta Soler
A
A
Lankenau Medical Research Center, Wynnewood, Pennsylvania 19096, USA.
Mullin
J M
JM
Knudsen
K A
KA
Marano
C W
CW
D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D015820:Cadherins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003571:Cytochalasin B / Q000494:pharmacology; D003584:Cytological Techniques; D017097:Electric Impedance; D018374:LLC-PK1 Cells / Q000187:drug effects* / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D010539:Permeability; D010750:Phosphoproteins / Q000378:metabolism; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D062826:Zonula Occludens-1 Protein
D000199:Actins; D015820:Cadherins; D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; D010750:Phosphoproteins; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein; D003571:Cytochalasin B