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Cell Tissue Res. 2007 Dec;330(3):427-35. Epub 2007 Oct 13.

C/EBP alpha knock-in hepatocytes exhibit increased albumin secretion and urea production.

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Department of Physiology, National University of Singapore, Blk MD9, 2 Medical Drive, Singapore 117597, Singapore.


The CCAAT/enhancer-binding protein alpha (C/EBP alpha) is essential for maintaining the differentiated state of hepatocytes in vivo. C/EBP alpha activates albumin transcription and coordinates the expression of multiple ornithine cycle enzymes involved in urea production. We have examined the effects of the C/EBP alpha knock-in gene on the mRNA and protein expression of genes involved in liver-specific functions, such as albumin and urea production. Albumin mRNA and protein levels are higher in knock-in hepatocytes compared with wild-type hepatocytes. mRNA levels for the ornithine cycle enzymes, namely arginase, carbamylphosphate synthetase 1, and ornithine transcarbamylase, also increase. Albumin secretion and urea production are sustained at higher levels in culture in knock-in hepatocytes. We have previously established that C/EBP alpha induces early liver glycogen storage in C/EBP alpha knock-in mice. Our present observations underline the importance of C/EBP alpha in liver metabolism and suggest that the induction of C/EBP alpha expression enhances hepatocyte function.

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