Apoptotic Cell Death Induced by Disruption of Epithelial Cell and Extracellular Matrix Interactions in Mouse Inner Medullary Collection Duct Cells.
- Author:
Jin Suk CHEON
1
;
Mi Young PARK
;
Yong Keun KIM
;
Sang Ho LEE
;
Jin Sup JUNG
Author Information
1. Department of Internal Medicine, Pusan Veterans Hospital, Pusan, Korea.
- Publication Type:Original Article
- Keywords:
mIMCD-3 cell;
Apoptosis;
Epidermal Epidermal growth factor (EGF);
PI-3 kinase
- MeSH:
Animals;
Apoptosis;
Cell Death*;
Epidermal Growth Factor;
Epithelial Cells*;
Extracellular Matrix*;
Mice*;
Mice, Transgenic;
Phosphatidylinositol 3-Kinase;
Phosphatidylinositol 3-Kinases;
Phosphotransferases
- From:Korean Journal of Nephrology
1999;18(1):37-45
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
Cell-matrix interactions have major effects upon phenotypic features such as gene regulation, cytoskeletal structure, differentiation, and aspects of cell growth control. Upon detachment from the matrix epithelial cells enter into programmed cell death and this cell detachment-induced apoptosis has been referred to as "anoikis". This study was undertaken to determine whether apoptosis is induced by inhibition of contact with extracellular matrix in mouse inner medullary collecting duct cells (mIMCD-3), what are signaling mechanisms of the process and whether EGF protects detachment-induced apoptosis. Upon detachment from the extracellular matrix, MDCK and mIMCD-3, which were derived from inner medulla of SV40 transgenic mouse, entered into programmed cell death as a time-dependent manner. Apoptotic cell death induced by cell detachment increased in serum-free medium, which was partly protected by the addition of epidermal growth factor (EGF). Ly294002 and wortmannin, inhibitors of phosphatidylinositol 3-kinase (PI 3-kinase), negated the EGF effect, whereas PD98059, a MEK inhibitor, did not. The addition of SB203580, an inhibitor of p38 kinase, did not protect apoptosis in suspended mIMCD-3 cells. These results indicate that apoptosis is induced by inhibition of contact with extracellular matrix in mouse inner medullary collecting duct cells and that PI 3-kinase, not MAPK, is a key mediator of the EGF-induced survival of renal epithelial cells in the absence of attachment.
