In:
Journal of Molecular Endocrinology, Bioscientifica, Vol. 33, No. 2 ( 2004-10), p. 445-458
Abstract:
Thyroid hormones regulate growth, development, differentiation, and metabolic processes by interacting with and activating thyroid hormone receptors and associated pathways. We investigated the triiodothyronine (T 3 ) modulation of gene expression, in human hepatocellular carcinoma cell lines, via a PCR-based cDNA subtraction method. Here we present further data on one of the T 3 -upregulated genes, fibronectin (FN). We demonstrate that the induction of FN protein expression by T 3 in TRα1 and TRβ1 over-expressing cells was time and dose-dependent at the mRNA and protein levels. Blockade of protein synthesis by cycloheximide almost completely inhibited the concomitant induction of FN mRNA by T 3 , indicating that T 3 indirectly regulates FN. Furthermore, nuclear-run on and FN promoter assay clearly can specifically increase the number of FN transcriptional demonstrated that the presence of T 3 initiations. In addition, we further confirmed that the up-regulation of FN by T 3 was mediated, at least in part, by transforming growth factor-β (TGF-β), because the induction of FN was blocked in a dose-dependent manner by the addition of TGF-β neutralizing antibody. In an effort to elucidate the we demonstrated the involvement of the signaling pathways involved in the activation of FN by T 3 , mitogen activated protein kinase/c-Jun N-terminal kinase/p38 MAPK (MAPK/JNK/p38) pathway. Although T 3 induces the expression of TGF-β, neither wild-type nor dominant-negative Smad3 or Smad4 over-expression affected the activation of FN by T 3 . Thus, we demonstrate that T 3 regulates FN gene expression indirectly at the transcriptional level, with the participation of the MAPK/JNK/p38 pathway and the TGF-β signaling pathway but independent of Smad3/4.
Type of Medium:
Online Resource
ISSN:
0952-5041
,
1479-6813
Language:
Unknown
Publisher:
Bioscientifica
Publication Date:
2004
detail.hit.zdb_id:
1478171-2
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