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Transforming growth factor Î² induction of insulin gene expression is mediated by pancreatic and duodenal homeobox geneâ1 in rat insulinoma cells
- Sayo, Yoshitaka, Hosokawa, Hitoshi, Imachi, Hitomi, Murao, Koji, Sato, Makoto, Wong, Norman C. W., Ishida, Toshihiko, Takahara, Jiro
- European journal of biochemistry 2000 v.267 no.4 pp. 971-978
- Western blotting, binding sites, gel electrophoresis, gene expression, genes, insulin, islets of Langerhans, messenger RNA, mutants, rats, transcription factors, transforming growth factor beta
- Although transforming growth factorâbeta (TGFâÎ²) stimulates pancreatic islet cells to synthesize and secret insulin, the mechanism underlying this effect is not known. To investigate this question, we examined the insulin promoter activity focusing on a transcription factor, pancreatic and duodenal homeobox geneâ1 (PDXâ1) that binds to the A3 element of the rat insulin promoter. Studies performed using the rat insulinoma cell line, INSâ1 showed that TGFâÎ² stimulation of endogenous insulin mRNA expression correlated with increased activity of a reporter construct containing the insulin promoter. A potential mechanism for this increase arose from, electrophoretic mobility shift assay showing that the nuclear extract from TGFâÎ² treated cells contained higher levels of A3 binding activity. Western blot analysis confirmed that PDXâ1 was increased in the nuclear extract from INSâ1 cells treated with TGFâÎ². As expected, a mutant insulin promoter that lacked the PDXâ1 binding site was not stimulated by TGFâÎ². In summary, the results of these studies show that TGFâÎ² stimulates the transcription of insulin gene and this action is mediated by the transcription factor, PDXâ1.