SELECTIVE TRANSCRIPTIONAL AUGMENTATION OF HEPATIC GENE-EXPRESSION IN THE RAT WITH HEYMANN NEPHRITIS

The synthesis of albumin and other hepatic proteins, many regulated as part of the acute phase response, is increased in the nephrotic syndrome. It has been postulated that synthesis of all proteins secreted by the liver is increased by the same mechanism in the nephrotic syndrome. However, the observation that synthesis of some apolipoproteins is not increased suggests that only a specific group of proteins may be similarly regulated in nephrosis. We measured synthesis of albumin and of two acute phase proteins, fibrinogen and alpha1-acid glycoprotein (alpha1-AG), in rats with Heymann nephritis (HN), their mRNA concentration in liver, and the rate of transcription of their genes by hepatic nuclei. Albumin and fibrinogen mRNA levels almost doubled in HN, but alpha1-AG mRNA was unchanged. Ribosomal RNA (28S) concentration and transcription were also increased significantly in HN. Transcription of albumin and fibrinogen also increased twofold, but transcription of alpha1-AG was unchanged. Fibrinogen and albumin synthesis each increased more than fourfold in HN and correlated with one another. In contrast alpha1-AG synthesis only increased by 50% and did not correlate with albumin synthesis. Both albumin and alpha1-AG were lost in the urine of HN, and their plasma concentrations were reduced. Fibrinogen was not lost in the urine and its plasma concentration was significantly increased in HN. Synthesis of a group of proteins including both positive acute phase (fibrinogen) and negative acute phase (albumin) proteins is increased transcriptionally in the nephrotic syndrome. Synthesis of other proteins is increased posttranscriptionally. Therefore, a coordinated group of hepatic proteins is similarly regulated in HN, and this is not due to the acute phase response. Furthermore, neither the change in plasma concentration of a specific protein nor the possibility that protein is lost in urine determines whether its synthesis will be changed at the transcriptional level.