2016
DOI: 10.1038/srep30215
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Osteopontin Deficiency Alters Biliary Homeostasis and Protects against Gallstone Formation

Abstract: The precipitation of excess biliary cholesterol as solid crystals is a prerequisite for cholesterol gallstone formation, which occurs due to disturbed biliary homeostasis. Biliary homeostasis is regulated by an elaborate network of genes in hepatocytes. If unmanaged, the cholesterol crystals will aggregate, fuse and form gallstones. We have previously observed that the levels of osteopontin (OPN) in bile and gallbladder were reduced in gallstone patients. However, the role and mechanism for hepatic OPN in chol… Show more

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Cited by 11 publications
(13 citation statements)
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“…OPN −/− mice was less susceptible to diet-induced gallstone than WT mice, which is consistent with our previous work ( 19 ). The body weight and gallbladder volume did not differ between the OPN −/− mice and WT mice fed with CD nor LD for 8 weeks.…”
Section: Discussionsupporting
confidence: 93%
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“…OPN −/− mice was less susceptible to diet-induced gallstone than WT mice, which is consistent with our previous work ( 19 ). The body weight and gallbladder volume did not differ between the OPN −/− mice and WT mice fed with CD nor LD for 8 weeks.…”
Section: Discussionsupporting
confidence: 93%
“…For the increased biliary bile acids content in LD-fed OPN −/− mice, we did not find the expression of intestinal genes involved in reabsorption of bile acids differ between two strains. The reason might be that OPN could influence the expression of the cytochrome P450, family 7, subfamily a, polypeptide 1, the rate limiting enzyme of bile acids synthesis, as we found in our previous study ( 19 ).…”
Section: Discussionmentioning
confidence: 63%
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“…In an effort to identify genes with the strongest potential to be involved in the development of GSD by a CNV-related mechanism, we highlight 23 genes involved in lipid metabolic process, which are expressed in the small intestine and exclusively affected by CNV in cases. Direct functional links between the candidate genes and the etiology of GSD is available for: the lipid transporter ATPase phospholipid transporting 8B1, (ATP8B1) gene [28], the RB transcriptional corepressor 1, (RB1) gene [37], the hepatocyte nuclear factor 1α (HNF1A) gene [38], the bile salt transporter gene sulfotransferase family 2 A member 1, (SULT2A1) gene [10], and the Apolipoprotein L1 and L2 (APOL1 and APOL2) involved in lipid transport. In addition, we note that the 23 candidate genes were enriched with 7 genes extremely intolerant to loss-of-function genetic variation (i.e., ALAS1, HNF1A, LYN, OCRL, PDHA1, RB1, and TBL1X; hypergeometric test p-value = 0.033) and variants within these genes are rarely found in the general population [39].…”
Section: Discussionmentioning
confidence: 99%
“…CNV burden analysis was performed by comparing the number of cases and controls with at least one CNV overlapping a member of a gene set of interest, as described [27,28]. To avoid bias, samples were counted only once, irrespectively of the number of CNVs found.…”
Section: Burden Analysismentioning
confidence: 99%