Biliary atresia--translational research on key molecular processes regulating biliary injury and obstruction.
نویسنده
چکیده
Biliary atresia is the most common cause of pathologic jaundice in young infants and results from the obstruction of the extrahepatic bile ducts by an inflammatory and fibro-obliterative process. Although the pathogenesis of the disease is multifactorial, recent patient- and animal-based studies began deciphering the molecular pathways involved in biliary injury and duct obstruction. Using large-scale genomics and immunostaining of livers from children with biliary atresia, investigators have discovered unique molecular signatures of dominant proinflammatory cytokines at the time of diagnosis. To study hypotheses generated from these patient-based studies, the anatomical and inflammatory profiles of a mouse model of rotavirus-induced biliary atresia were analyzed and found to share striking similarities with the human profiles. Then, using these mice in mechanistic studies, interferon-gamma (IFNgamma) has been shown to regulate the biliary tropism of lymphocytes to the biliary system, and to play a critical role in the inflammatory obstruction of extrahepatic bile ducts. The ability to combine human studies with a laboratory model of neonatal biliary injury and obstruction opens a new era of opportunities to advance the field of biliary atresia, and to develop new therapeutic strategies to improve long-term outcome with the native liver of children with biliary atresia.
منابع مشابه
The Role of Appendix in the Management of Biliary Atresia Associated with Bowel Atresia
Biliary atresia is characterized by the progressive obliteration of extra- and intrahepatic biliary duct system leading to the obstruction of bile flow in infancy. The cause(s) of biliary atresia remain unclear and many surgical options for bypassing the atretic segment have been described.1-3 Biliary atresia may be associated with small bowel atresia. The surgical interventions for biliary dr...
متن کاملUltrasonographic Triangular Cord Sign and Gallbladder Abnormality in Diagnosis of Biliary Atresia
Introduction: Early diagnosis of biliary atresia is very important for better outcome of treatment. Ultrasonography is one of the diagnostic tools for early differentiation of biliary atresia from other causes of neonatal cholestasis. It has been reported that triangular cord sign (TACS) in sonography is a reliable sign for diagnosis of biliary atresia. The aim of this study was to re-assess ...
متن کاملNatural Killer Cells Promote Long-Term Hepatobiliary Inflammation in a Low-Dose Rotavirus Model of Experimental Biliary Atresia
UNLABELLED Biliary atresia is a rapidly progressive obstructive cholangiopathy of infants. Mechanistic studies in the mouse model of Rhesus rotavirus (RRV)-induced biliary atresia have linked the importance of effector lymphocytes to the pathogenesis of extrahepatic bile duct (EHBD) injury and obstruction in experimental biliary atresia; however, studies of the progressive liver injury have bee...
متن کاملNeonatal NK cells target the mouse duct epithelium via Nkg2d and drive tissue-specific injury in experimental biliary atresia.
Biliary atresia is a neonatal obstructive cholangiopathy that progresses to end-stage liver disease. Although the etiology is unknown, a neonatal adaptive immune signature has been mechanistically linked to obstruction of the extrahepatic bile ducts. Here, we investigated the role of the innate immune response in the pathogenesis of biliary atresia. Analysis of livers of infants at diagnosis re...
متن کاملToll-Like Receptors in Secondary Obstructive Cholangiopathy
Secondary obstructive cholangiopathy is characterized by intra- or extrahepatic bile tract obstruction. Liver inflammation and structural alterations develop due to progressive bile stagnation. Most frequent etiologies are biliary atresia in children, and hepatolithiasis, postcholecystectomy bile duct injury, and biliary primary cirrhosis in adults, which causes chronic biliary cholangitis. Bil...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Chang Gung medical journal
دوره 29 3 شماره
صفحات -
تاریخ انتشار 2006