Transforming growth factor-beta 1 inhibits nucleosomal fragmentation in human keratinocytes following loss of adhesion.
We have investigated the role of transforming growth factor-beta 1 (TGF-beta 1) in suspension-induced programmed cell death of cultured human keratinocytes. Suspension of keratinocytes in semisolid medium induces TGF-beta 1 mRNA levels and synthesis of bioactive TGF-beta 1 protein. Concomitant with the suspension-induced increase in secreted TGF-beta 1 levels, steady state mRNA levels for c-myc are decreased. Both exogenously added and endogenously produced TGF-beta 1 attenuate suspension-induced nucleosomal fragmentation in keratinocytes. We propose that TGF-beta 1 may function to protect keratinocytes from DNA fragmentation following loss of cell-substratum and/or cell-cell contact. Taken together, our findings suggest that loss of cell-substratum and/or cell-cell adhesion is an important component of an apoptotic signal transduction cascade regulated by TGF-beta 1 in normal human stratified squamous epithelia.
Department of Pathology, Environmental Toxicology Center, Madison, Wisconsin 53706, USA.
K F
KF
Sachsenmeier
N
N
Sheibani
S J
SJ
Schlosser
B L
BL
Allen-Hoffmann
D002448:Cell Adhesion; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D007231:Infant, Newborn; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D009707:Nucleosomes; D016212:Transforming Growth Factor beta; D004247:DNA