Sucrase-isomaltase gene expression is inhibited by mutant hepatocyte nuclear factor (HNF)-1α and mutant HNF-1β in Caco-2 cells

Hepatocyte nuclear factor (HNF)-1 alpha and HNF-1 beta are concerned in sucrase-isomaltase (SI) gene expression, and directly bind two sites (SIF2. SIF3) of file promoter of the SI gene. However, it is not completely clear Chat HNF-1 alpha and HNF-1 beta play a role in regulation of SI gene expression. To clarify mechanisms of SI gene expression regulated by HNF-1 alpha and HNF-1 beta, we established four stable cell lines based on enterocyte-like cell line Caco-2, in which wild HNF-1 alpha or wild HNF-1 beta. or else Mutant HNF-1 alpha T539fsdelC or mutant HNF-1 beta R177X was overexpressed. In the HNF-1 alpha T539fsdelC cells and HNF-1 beta R177X cells, but not in the wild HNF-1 alpha cells and wild HNF-1 beta cells. SI gene expression and enzyme activity were significantly diminished compared with that in Caco-2 cells. Moreover, to clarify whether or not stable cell differentiation was influenced by overexpression of these transgenes, alkaline phosphatase (ALP) gene expression and enzyme activity were measured. There were no changes in ALP gene expression or enzyme activity in these cells. These observations suggest that mutant HNF-1 alpha T539fsdelC and mutant HNF-1 beta R177X inhibits SI gene at the transcriptional level. resulting in decreased SI enzyme activity in Caco-2 cells. We propose that both HNF-1 alpha and HNF-1 beta would contribute to Constitutive expression of the SI gene in the differentiated state ill Caco-2 cells.