Transforming Growth Factor 81 Positively Regulates Its Own Expression in Normal and Transformed Cells *

Transforming growth factor 81 (TGF-81) regulates the growth, differentiation, or function of nearly all cell types. We now report hat TGF-81 increases steady-state levels of its own message in six different normal and transformed cells in culture. Accumulation of TGF-81 mRNA can be detected by Northern blot analysis within 3 h of addition of the peptide to cells, and enhanced message levels persist as long as TGF81 is present in the culture medium. This autoinduction is half-maximal at -10 PM TGF-81, and maximal stimulation corresponds to a 2-3-fold increase in transcript levels. In normal rat kidney cells, the rise in TGF-81 mRNA is actinomycin D-sensitive and is accompanied by a parallel (-3-fold) increase in secretion of TGF-81 protein in the culture medium of treated cells, as detected by immunoprecipitation of biosynthetically labeled S6S-labeled TGF-81 using specific anti-TGF-81 antibodies. Treatment of normal rat kidney cells with either epidermal growth factor or platelet-derived growth factor also results in an increase in TGF-81 mRNA (2-3-fold), although epidermal growth factor and TGF-81 appear to act via distinct mechanisms since their combined effects are greater than additive.