Cholic Acid Induces a Cftr Dependent Biliary Secretion and Liver Growth Response in Mice

نویسندگان

  • Frank A. J. A. Bodewes
  • Marcel J. Bijvelds
  • Willemien de Vries
  • Juul F. W. Baller
  • Annette S. H. Gouw
  • Hugo R. de Jonge
  • Henkjan J. Verkade
چکیده

The cause of Cystic fibrosis liver disease (CFLD), is unknown. It is well recognized that hepatic exposure to hydrophobic bile salts is associated with the development of liver disease. For this reason, we hypothesize that, CFTR dependent variations, in the hepatic handling of hydrophobic bile salts, are related to the development CFLD. To test our hypothesis we studied, in Cftr-/- and control mice, bile production, bile composition and liver pathology, in normal feeding condition and during cholate exposure, either acute (intravenous) or chronic (three weeks via the diet). In Cftr-/- and control mice the basal bile production was comparable. Intravenous taurocholate increased bile production to the same extent in Cftr-/- and control mice. However, chronic cholate exposure increased the bile flow significantly less in Cftr-/- mice than in controls, together with significantly higher biliary bile salt concentration in Cftr-/- mice. Prolonged cholate exposure, however, did not induce CFLD like pathology in Cftr-/- mice. Chronic cholate exposure did induce a significant increase in liver mass in controls that was absent in Cftr-/- mice. Chronic cholate administration induces a cystic fibrosis-specific hepatobiliary phenotype, including changes in bile composition. These changes could not be associated with CFLD like pathological changes in CF mouse livers. However, chronic cholate administration induces liver growth in controls that is absent in Cftr-/- mice. Our findings point to an impaired adaptive homeotrophic liver response to prolonged hydrophobic bile salt exposure in CF conditions.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

AGI Mar 39/3

Wang, David Q.-H., Frank Lammert, David E. Cohen, Beverly Paigen, and Martin C. Carey. Cholic acid aids absorption, biliary secretion, and phase transitions of cholesterol in murine cholelithogenesis. Am. J. Physiol. 276 (Gastrointest. Liver Physiol. 39): G751–G760, 1999.—Cholic acid is a critical component of the lithogenic diet in mice. To determine its pathogenetic roles, we fed chow or 1% c...

متن کامل

Cholic acid aids absorption, biliary secretion, and phase transitions of cholesterol in murine cholelithogenesis.

Cholic acid is a critical component of the lithogenic diet in mice. To determine its pathogenetic roles, we fed chow or 1% cholesterol with or without 0.5% cholic acid to C57L/J male mice, which because of lith genes have 100% gallstone prevalence rates. After 1 yr on the diets, we measured bile flow, biliary lipid secretion rates, hepatic cholesterol and bile salt synthesis, and intestinal cho...

متن کامل

Protein Kinase Cβ: Linking Intestine Fibroblast Growth Factor 15 to Hepatic Extracellular Signal Regulated Kinase 1/2 Signaling in Bile Acid and Cholesterol Homeostasis

holesterol homeostasis is maintained by balancing Ccholesterol input from diet and de novo synthesis and output via conversion to bile acids in the liver and sterol hormones in steroidogenic tissues. About 50% of cholesterol is converted to bile acids, which facilitates biliary secretion of another 40% of cholesterol. Thus, bile acid synthesis and metabolism is critical for maintaining wholebod...

متن کامل

Expression of liver plasma membrane transporters in gallstone-susceptible and gallstone-resistant mice.

We tested the hypothesis that differential expression of liver plasma membrane transporters might account for variations in biliary lipid secretion rates between gallstone-susceptible C57L/J and gallstone-resistant AKR/J mice. Plasma membrane fractions and total RNA isolated from livers of mice fed with a control or lithogenic (15% fat/1.25% cholesterol/0.5% cholic acid) diet were used for meas...

متن کامل

CFTR and pHi regulation.

TO THE EDITOR: Using enteroids grown from crypts obtained from cystic fibrosis transmembrane receptor (CFTR) transgenic mice, Walker et al. (8) measured intracellular pH (pHi) regulation using a standard fluorescent dye-loading methodology. Based on results, the authors concluded that crypts originating in CFTR mice had elevated resting pHi and resistance to acidification. The authors stated th...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 10  شماره 

صفحات  -

تاریخ انتشار 2015