Abstract
The present study has investigated the relative levels and interconversion of latent and active forms of transforming growth factor-beta 1 (TGF-beta 1) in human thyroid follicular cell cultures derived from sporadic non-toxic goitres. Northern blotting of RNA extracted from 72-h cultures revealed a 2.5 kb mRNA transcript hybridizing with a cDNA probe for latent TGF-beta 1, the intensity of which was doubled in cells exposed to NaI (10 mumol/l). Radioreceptor assay of follicular cell-conditioned medium for TGF-beta 1 content confirmed a similar enhancing effect of iodide. The endogenous active component of TGF-beta 1 present in conditioned medium represented only a minor fraction of the total TGF-beta 1 content, this fraction was not enhanced by exposure of follicular cells to iodide. The low level of endogenous active TGF-beta 1 in medium conditioned by either control or iodide-treated cells was confirmed by immunoadsorption with a precipitating antiserum against active TGF-beta 1, when such cells failed to show a reversal of the iodide-induced decrease in [methyl-3H]thymidine incorporation into trichloroacetic acid-precipitable material. In contrast to the inhibitory effect of iodide on de novo DNA synthesis, which appeared not to reflect an increase in active TGF-beta 1, the inhibitory effects of plasminogen (100 mg/l) or plasmin (2000 U/l) on [methyl-3H]thymidine incorporation into thyroid cells were reversible by TGF-beta 1 immunoadsorption. This provides evidence that the plasmin-mediated inhibition of DNA synthesis in thyroid follicular cells may be attributed to the growth-regulating action of an increased level of activated TGF-beta 1.(ABSTRACT TRUNCATED AT 250 WORDS)
Published Version
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