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22 December 2011

Osteopontin and integrin are involved in cholesterol gallstone formation

Lin YangACEF, Jin-hong ChenABD, Duan CaiDF, Li-ying WangBD, Xi-liang ZhaBF

DOI: 10.12659/MSM.882194

Med Sci Monit 2012; 18(1): BR16-23

Abstract

Background: This study aimed to investigate the role of osteopontin and its receptor, integrin alphav, in gallstone formation using human tissue specimens and a guinea pig lithogenic model.
Material/Methods: The nucleation role of osteopontin was determined in patients’ and normal gallbladder bile samples in vitro. Normal gallbladder was the control, and gallstone gallbladders were divided into group I (with normal epithelia) and group II (with degenerated epithelia) based on pathology change. Immunostaining, mRNA and protein expressions of osteopontin and integrin alphav were analyzed. The animals were randomly divided into a lithogenic diet group and a normal diet group; the osteopontin mRNA expression in gallbladder and liver and osteopontin concentrations were determined.
Results: Osteopontin prolonged nucleation time and inhibited the pro-nucleating role induced by calcium in human bile in vitro. Immunostaining for osteopontin and integrin alphav in human gallbladder tissues showed a higher reactivity in Group I than control group and Group II. The immunostaining in Group II was weaker than control group; similar results were observed for mRNA and protein expression of osteopontin and integrin alphav. In the animal assay, the mRNA expression and concentration of osteopontin in gallbladder and liver gradually increased at initial stages and decreased in later stages. The concentrations of osteopontin in bile and serum of guinea pig showed similar trends.
Conclusions: Our results suggest that osteopontin is involved in cholesterol gallstone formation, and the role of osteopontin might correlate with integrin alphav and calcium.

Keywords: Integrin alphaV - metabolism, Guinea Pigs, Gallstones - pathology, Gallbladder - metabolism, Diet, Calcium - metabolism, Blotting, Western, Bile - metabolism, Animals, Liver - metabolism, Osteopontin - metabolism, Reverse Transcriptase Polymerase Chain Reaction

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Medical Science Monitor eISSN: 1643-3750
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