Differential Expression of Transforming Growth Factors a and ft in Rat Intestinal Epithelial Cells

Expression of transforming growth factor a (TGF a), and transforming growth factor 13 (TGF ,1) was assessed in isolated primary rat intestinal epithelial cells as well as a rat intestinal crypt cell-derived cell line (IEC-6). A gradient in TGF ,8 was present, with high concentrations of a 2.5-kb transcript found in undifferentiated crypt cells and progressively lower amounts of the TGF 13 transcript in increasingly differentiated villus cell populations. In contrast, the concentration of 4.5-kb TGF a transcript was higher in differentiated villus cells than in mitotically active, undifferentiated populations of crypt epithelial cells. The concentrations of transforming growth factors a and 13 as determined by radioreceptor binding inhibition assay and direct assessment of transforming growth factor biological activity correlated with Northern blot analysis. Although gradients in the expression of the TGFs were present, equivalent binding was observed in the different intestinal cell populations when assessed with 125I-TGF 13 and 125I-EGF (TGF a). No EGF transcripts were detected in any intestinal cell population, suggesting that the true ligand of the EGF receptor was TGF a. IEC-6 cells expressed both TGF a and TGF 1 transcripts. In addition to the transcripts identified in the primary intestinal cells, this cell line contained an additional larger TGF a transcript (4.8 kb) and smaller TGF 13 transcripts (2.2 and 1.8 kb). TGF a and TGF 13 may play a significant role in the regulation of the balance between proliferative and differentiated cell compartments in the intestinal epithelium through both autocrine and paracrine mechanisms.