TGF-beta blocks early but not late differentiation-specific gene expression and morphologic differentiation of 3T3 T proadipocytes.
Transforming growth factor-beta (TGF-beta) inhibits morphologic differentiation of BALB/c 3T3 T cells as well as other proadipocyte models. Our prior studies suggested that TGF-beta may act only during the early stages of differentiation induction. However, we did not determine whether TGF-beta was differentially effecting expression of any of the various differentiation-specific genes or if it could cause down-regulation of these genes in differentiated cells. Therefore, in the current study we tested the effects of exogenous TGF-beta (0.01-5.0 ng/ml) on morphologic differentiation and on differentiation-dependent gene expression (Northern and slot blot analyses) at various times during differentiation. When induced to differentiate, 3T3 T cells first undergo predifferentiation growth arrest and from this state molecular, biochemical, and morphological differentiation proceeds. Here it was found that when added prior to the onset of differentiation, TGF-beta was a potent inhibitor or morphologic differentiation as well as of the expression of differentiation-specific genes such as lipoprotein lipase (LPL) and glycerol-3-phosphate dehydrogenase (GPD). However, once morphologic differentiation began, TGF-beta was ineffective in blocking differentiation. In addition, exposure of fully differentiated cells to TGF-beta for up to 72 hours caused no decrease of differentiation-specific genes and even a 7-day treatment caused no morphologic dedifferentiation. Tumor necrosis factor also had no detectable effect on fully differentiated cells.
Sparks
R L
RL
Department of Cell Biology and Anatomy, School of Medicine, Oregon Health Sciences University, Portland 97201-3098.
Allen
B J
BJ
Strauss
E E
EE
D016475:3T3 Cells; D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D000818:Animals; D015152:Blotting, Northern; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005993:Glycerolphosphate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism; D051379:Mice; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016212:Transforming Growth Factor beta; D005993:Glycerolphosphate Dehydrogenase; D008071:Lipoprotein Lipase