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Transforming growth factor-beta 1 inhibits nucleosomal fragmentation in human keratinocytes following loss of
K F Sachsenmeier1, N Sheibani, S J Schlosser
1Department of Pathology, Environmental Toxicology Center, Madison, Wisconsin 53706, USA.
Abstract:
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.