scholarly journals Liver Expression of Sulphotransferase 2A1 Enzyme Is Impaired in Patients with Primary Sclerosing Cholangitis: Lack of the Response to Enhanced Expression of PXR

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Ewa Wunsch ◽  
Marta Klak ◽  
Urszula Wasik ◽  
Malgorzata Milkiewicz ◽  
Malgorzata Blatkiewicz ◽  
...  
Keyword(s):  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Pregnane X Receptor ◽  
Biliary Cirrhosis ◽  
Pathogenic Role ◽  
Enhanced Expression ◽  
Hepatoprotective Effects ◽  
And Control ◽  
Affymetrix Gene Chip ◽  
Disease Specific

Background/Aim. Sulphotransferase 2A1 (SULT2A1) exerts hepatoprotective effects. Transcription ofSULT2A1gene is induced by pregnane-X-receptor (PXR) and can be repressed by miR-378a-5p. We studied the PXR/SULT2A1 axis in chronic cholestatic conditions: primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC).Materials/Methods. Western-blot/PCRs for SULT2A1/PXR were performed in PSC (n=11), PBC (n=19), and control liver tissues (n=19).PXRandSULT2A1mRNA was analyzed in intestinal tissues from 22 PSC patients. Genomic DNA was isolated from blood of PSC patients (n=120) and an equal number of healthy volunteers. Liver miRNA expression was evaluated using Affymetrix-Gene-Chip miRNA4.0.Results. Increased PXR protein was observed in both PSC and PBC compared to controls and was accompanied by a significant increase of SULT2A1 in PBC but not in PSC. Decreased expression ofSULT2A1mRNA was also seen in ileum of patients with PSC. Unlike PBC, miRNA analysis in PSC has shown a substantial increase in liver miR-378a-5p.Conclusions.PSC is characterized by disease-specific impairment of SULT2A1 expression following PXR activation, a phenomenon which is not noted in PBC, and may account for the impaired hepatoprotection in PSC. miRNA analysis suggests that SULT2A1 expression in PSC may be regulated by miR-378a-5p, connoting its pathogenic role.

Disease specific alterations of the bile-duct derived biliary proteome in primary sclerosing cholangitis

2013 ◽  
Vol 51 (08) ◽  
Author(s):  
C Rupp ◽  
K Bode ◽  
Y Schäfer ◽  
KH Weiss ◽  
P Schirmacher ◽  
...  
Keyword(s):  
Bile Duct ◽  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Disease Specific

Primary Sclerosing Cholangitis

2015 ◽  
Author(s):  
Udayakumar Navaneethan
Keyword(s):  
Differential Diagnosis ◽  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Biliary Tree ◽  
Biliary Cirrhosis ◽  
Extrahepatic Bile Ducts ◽  
Biliary Stasis ◽  
Inflammatory Bowel ◽  
Direct Peroral Cholangioscopy ◽  
Secondary Biliary Cirrhosis

Primary sclerosing cholangitis (PSC) is a chronic progressive cholestatic disease characterized by inflammation and fibrosis that may involve the entire biliary tree. The fibrosis causes diffuse narrowing of the intrahepatic and extrahepatic bile ducts, and the resulting biliary stasis leads to secondary biliary cirrhosis and associated complications. This review addresses PSC through its epidemiology, etiopathogenesis, diagnosis, differential diagnosis, management, complications, and prognosis. Figures show pouchoscopy, liver biopsy, and endoscopic retrograde cholangiopancreatography; direct peroral cholangioscopy visualization of cholangiocarcinoma; and algorithms depicting diagnosis of cholangiocarcinoma and screening for inflammatory bowel disease (IBD) in patients with PSC. Tables list characteristics of IBD in PSC, prevalence of antibodies in PSC, differential diagnosis of PSC, diagnostic approach in PSC, and risk of cancers in PSC. This review contains 6 highly rendered figures, 5 tables, and 91 references. 

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