کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6101330 1211104 2015 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Research ArticleActivation of biliary tree stem cells within peribiliary glands in primary sclerosing cholangitis
ترجمه فارسی عنوان
مقدمه مقاله: فعال سازی سلول های بنیادی درون مجرای صفراوی در غدد لنفاوی در کلانژیت اسکلروزیس اولیه
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های گوارشی
چکیده انگلیسی

Background & AimsPrimary sclerosing cholangitis (PSC) is characterised by fibro-stenosing strictures involving extrahepatic and/or large intrahepatic bile ducts. Mechanisms leading to bile duct injury are poorly understood. We aimed to study the biliary tree stem cell compartment located in peribiliary glands of extrahepatic and large intrahepatic bile ducts and its role in the pathogenesis of biliary fibrosis in PSC.MethodsSpecimens containing extrahepatic or large intrahepatic bile ducts were obtained from normal liver (n = 6), liver explants from patients with PSC (n = 11), and primary biliary cirrhosis (n = 6). Specimens were processed for histology, immunohistochemistry and immunofluorescence.ResultsIn PSC samples, progressive hyperplasia and mucinous metaplasia of peribiliary glands were observed in large ducts with fibrosis, but not in inflamed ducts without fibrosis. Peribiliary gland hyperplasia was associated with progressive biliary fibrosis and the occurrence of dysplastic lesions. Hyperplasia of peribiliary glands was determined by the expansion of biliary tree stem cells, which sprouted towards the surface epithelium. In PSC, peribiliary glands and myofibroblasts displayed enhanced expression of Hedgehog pathway components. Peribiliary glands in ducts with onion skin-like fibrosis expressed epithelial-to-mesenchymal transition traits associated with components of Hedgehog pathway, markers of senescence and autophagy.ConclusionsThe biliary tree stem cell compartment is activated in PSC, its activation contributes to biliary fibrosis, and is sustained by the Hedgehog pathway. Our findings suggest a key role for peribiliary glands in the progression of bile duct lesions in PSC and could explain the associated high risk of cholangiocarcinoma.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Hepatology - Volume 63, Issue 5, November 2015, Pages 1220-1228
نویسندگان
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