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Penn researchers find a new role for a 'Foxy Old Gene'
Date:8/1/2008

PHILADELPHIA Researchers at the University of Pennsylvania School of Medicine have discovered that a protein called FOXA2 controls genes that maintain the proper level of bile in the liver. FOXA2 may become the focus for new therapies to treat diseases that involve the regulation of bile salts. The study was published online this week in Nature Medicine.

Bile, although made in the liver, is stored in the gall bladder and transported through ducts to the small intestine where it helps to digest fats from food. Bile salts, chemicals in bile that help digest fats and also keep cholesterol dissolved in the bile, are reabsorbed from the intestine and returned to the liver where they are broken up. The liver maintains a balance of bile salts by degrading old bile salts and synthesizing new ones. Problems arise when too many bile salts accumulate in the liver.

Diseases of bile regulation, such as primary sclerosing cholangitis (PSC), are characterized by problems with bile transport from the liver to the gut. The researchers found that in both children with biliary atresia and adults with PSC, syndromes of different etiologies, expression of FOXA2 in the liver is severely reduced. FOXA2 regulates expression of transporter proteins responsible for moving bile out of the liver, as well as several enzymes that function in bile acid detoxification. The study suggests that strategies to maintain FOXA2 expression might be a novel therapeutic goal.

In PSC, blockage of bile transport leads to inflammation of the bile duct and, over time, liver damage. The causes of PSC and related syndromes are not known, but may be autoimmune-related. PSC is associated with an increased risk of liver cirrhosis and liver cancer. Biliary atresia is a birth defect in which the bile ducts do not have normal openings, preventing bile from leaving the liver. The condition causes jaundice and cirrhosis of the liver.

Senior author Klaus Kaestner, PhD
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Contact: Karen Kreeger
karen.kreeegr@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

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