TGF‐β blocks early but not late differentiation‐specific gene expression and morphologic differentiation of 3T3 T proadipocytes

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Abstract
Transforming growth factor-β (TGF-β) inhibits morphologic differentiation of BALB/c 3T3 T cells as well as other proadipocyte models. Our prior studies suggested that TGF-β may act only during the early stages of differentiation induction. However, we did not determine whether TGF-β 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-β (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-β was a potent inhibitor of 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-β was ineffective in blocking differentiation. In addition, exposure of fully differentiated cells to TGF-β 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.