ABSTRACT
Erythropoietic protoporphyria (EPP) is a rare inherited disorder of porphyrin metabolism that can cause liver damage and cholestatic hepatocellular failure. We report a case of EPP in a teenaged male who underwent liver biopsy for investigation of liver dysfunction of unknown cause. The diagnosis was not made until a re-biopsy approximately three years later, when the patient presented with recurrent skin lesions and elevated blood and urinary protoporphyrin levels. The liver biopsies contained brownish deposits that exhibited birefringence under polarized light and porphyrin fluorescence under fluorescence spectroscopy. EPP should be considered in young patients with unexplained liver dysfunction, skin symptoms, and seasonal changes in symptoms. Fluorescence spectroscopy of liver biopsy tissue can be a useful tool in the diagnosis of EPP.
ABSTRACT
BACKGROUND AND AIM: It would be of clinical importance to clarify molecular mechanisms of cholangiocytes proliferation for the treatment of intractable cholestatic diseases. The aim of this study was to elucidate gene expression profiling in the whole liver of bile duct ligated (BDL) rats using microarray analysis. In addition, the localization and time course of up-regulated expression of vascular endothelial growth factor (VEGF) was investigated. METHODS: Male Sprague-Dawley rats were used. The whole liver was removed from BDL and sham-operated rats at day 2 after the procedure, and microarray analysis was performed using an array on which 3757 rat cDNA clones spotted. The up-regulation of VEGF expression was investigated by RT-PCR using livers at day 1, 2, 4 and 7, and immunoblotting and immunohistochemistry at day 2. RESULTS: Marked proliferation of bile ducts was observed in livers of BDL rats. By microarray analysis, 38 up-regulated and 17 down-regulated transcripts were detected in whole liver of the BDL rat. The expression of VEGF-A was significantly elevated in the BDL rats at day 2; the VEGF-A/GAPDH ratio was 4.030 +/- 2.493 in BDL rats and 1.159 +/- 0.125 in sham-operated rats (P = 0.0330). The up-regulation of VEGF-A expression was maximal at day 2. Immunoblotting also demonstrated up-regulated expression of VEGF-A at the protein level. Immunostaining of VEGF revealed that the expression was evident in hepatocytes adjacent to the portal tracts, and scarcely observed in hepatocytes at the centrilobular area or cholangiocytes. CONCLUSION: Gene expression profiling in the whole liver of the BDL rats revealed 38 up-regulated and 17 down-regulated transcripts. In addition, the up-regulated expression of VEGF was mainly observed in hepatocytes surrounding to the portal tracts.
