Intestinal synthesis and secretion of bile salts as an adaptation to developmental biliary atresia in the sea lamprey
Autor: | Huiyong Wang, Yu Wen Chung-Davidson, Chu Yin Yeh, Ke Li, Weiming Li |
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Rok vydání: | 2012 |
Předmět: |
medicine.medical_specialty
Taurine Cirrhosis Cholesterol 7 alpha-hydroxylase Polymerase Chain Reaction Mass Spectrometry Bile Acids and Salts chemistry.chemical_compound Cholestasis Biliary atresia Biliary Atresia Internal medicine medicine Animals Petromyzon Intestinal Mucosa Cholesterol 7-alpha-Hydroxylase Multidisciplinary Mucous Membrane biology Lamprey Biological Sciences medicine.disease biology.organism_classification Taurocholic acid Fibrosis Perfusion Endocrinology chemistry Liver Liver function Chromatography Thin Layer Chromatography Liquid |
Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 109(28) |
ISSN: | 1091-6490 |
Popis: | Bile salt synthesis is a specialized liver function in vertebrates. Bile salts play diverse roles in digestion and signaling, and their homeostasis is maintained by controlling input (biosynthesis) and intestinal conservation. Patients with biliary atresia (i.e., obliteration of the biliary tree) suffer liver fibrosis and cirrhosis. In contrast, sea lamprey thrives despite developmental biliary atresia. We discovered that the sea lamprey adapts to biliary atresia through a unique mechanism of de novo synthesis and secretion of bile salts in intestine after developmental biliary atresia, in addition to known mechanisms, such as the reduction of bile salt synthesis in liver. During and after developmental biliary atresia, expression of cyp7a1 in intestine increased by more than 100-fold ( P < 0.001), whereas in liver it decreased by the same magnitude ( P < 0.001). Concurrently, bile salt pools changed in similar patterns and magnitudes in these two organs and the composition shifted from C24 bile alcohol sulfates to taurine-conjugated C24 bile acids. In addition, both in vivo and ex vivo experiments showed that aductular sea lamprey secreted taurocholic acid into its intestinal lumen. Our results indicate that the sea lamprey, a jawless vertebrate, may be in an evolutionarily transitional state where bile salt synthesis occurs in both liver and intestine. Understanding the molecular basis of these mechanisms may shed light on the evolution of bile salt synthesis and possible therapy for infant biliary atresia. |
Databáze: | OpenAIRE |
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