Involvement of osteopontin as a core protein in cholesterol gallstone formation

Ichikawa, Hideaki; Imano, Motohiro; Takeyama, Yoshifumi; Shiozaki, Hitoshi; Ohyanagi, Harumasa

doi:10.1007/s00534-009-0043-4

Cited by 15 publications

(15 citation statements)

References 29 publications

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“…BECAUSE SEVERAL BILIARY proteins have been detected from human gallbladder bile and determined to be factors affecting cholesterol crystal nucleation, 3–12 the concept that cholesterol gallstone depends on an imbalance of the pro‐nucleation and anti‐nucleation factors has been raised. OPN expression has been detected in human GB, and it might correlatewith gallstone formation, 16,24 In our study, results showed that OPN could inhibit the cholesterol crystal nucleation in MB and human GB in vitro . This anti‐nucleation role showed the dose‐dependent property and OPN played the anti‐nucleation role in physiological concentration.…”

Section: Discussionsupporting

confidence: 49%

“…O.D., optical density. with gallstone formation, 16,24 In our study, results showed that OPN could inhibit the cholesterol crystal nucleation in MB and human GB in vitro. This antinucleation role showed the dose-dependent property and OPN played the anti-nucleation role in physiological concentration.…”

Section: B Ecause Several Biliary Proteins Have Beenmentioning

confidence: 53%

“…Furthermore, we examined the mRNA and protein expression of OPN in human gallbladder, and the results showed that OPN mRNA and protein expression were lower in lithogenic gallbladder than in normal tissue. Recently, Ichikawa et al 24 demonstrated the OPN level varied from sites of calculus on the gallbladder wall. Therefore, we considered that the pathological gallbladder could affect the expression of OPN in bile.…”

Section: Figurementioning

confidence: 99%

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Osteopontin plays an anti‐nucleation role in cholesterol gallstone formation

Yang

Chen

Cai

et al. 2011

Hepatology Research

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Section: Discussionsupporting

confidence: 49%

Section: B Ecause Several Biliary Proteins Have Beenmentioning

confidence: 53%

Section: Figurementioning

confidence: 99%

See 1 more Smart Citation

Osteopontin plays an anti‐nucleation role in cholesterol gallstone formation

Yang

Chen

Cai

et al. 2011

Hepatology Research

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“…It exists as a component of the extracellular matrix and as a soluble cytokine. Osteopontin is shown to be involved in cholesterol and pigment gallstone 48, 49. In addition, we also identified other putative pro‐nucleation proteins including aminopeptidase N, orosomucoid 1, orosomucoid 2 and haptoglobin 1 19.…”

Section: Resultsmentioning

confidence: 81%

Comprehensive proteomic analysis of human bile

et al. 2011

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Bile serves diverse functions from metabolism to transport. In addition to acids and salts, bile is composed of proteins secreted or shed by the hepatobiliary system. Although there have been previous efforts to catalog biliary proteins, an in-depth analysis of the bile proteome has not yet been reported. We carried out fractionation of non-cancerous bile samples using a multipronged approach (SDS-PAGE, SCX and OFFGEL) followed by MS analysis on an LTQ-Orbitrap Velos mass spectrometer using high resolution at both MS and MS/MS levels. We identified 2552 proteins - the largest number of proteins reported in human bile till date. To our knowledge, there are no previous studies employing high-resolution MS reporting a more detailed catalog of any body fluid proteome in a single study. We propose that extensive fractionation coupled to high-resolution MS can be used as a standard methodology for in-depth characterization of any body fluid. This catalog should serve as a baseline for the future studies aimed at discovering biomarkers from bile in gallbladder, hepatic, and biliary cancers.

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“…Furthermore, we found that OPN and integrin αv displayed a similar change at the molecular level. Recently, Ichikawa et al [34] demonstrated that the OPN level varied from sites of calculous gallbladder walls, suggesting that OPN plays a different role in gallstone formation. These findings suggest that the functional and structural changes in gallbladders could affect the secretion of OPN and its contents in gallbladder bile, which may be involved in gallstone formation through different pathways in different stage of gallstone disease.…”

Section: Discussionmentioning

confidence: 99%

Osteopontin and integrin are involved in cholesterol gallstone formation

et al. 2012

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SummaryBackgroundThis study aimed to investigate the role of osteopontin and its receptor, integrin αv, in gallstone formation using human tissue specimens and a guinea pig lithogenic model.Material/MethodsThe 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 αv 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.ResultsOsteopontin prolonged nucleation time and inhibited the pro-nucleating role induced by calcium in human bile in vitro. Immunostaining for osteopontin and integrin αv 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 αv. 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.ConclusionsOur results suggest that osteopontin is involved in cholesterol gallstone formation, and the role of osteopontin might correlate with integrin αv and calcium.

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Involvement of osteopontin as a core protein in cholesterol gallstone formation

Abstract: These results suggest that Opn is possibly involved as a core protein in the formation of cholesterol gallstones.

Cited by 15 publications

References 29 publications

Osteopontin plays an anti‐nucleation role in cholesterol gallstone formation

Osteopontin plays an anti‐nucleation role in cholesterol gallstone formation

Comprehensive proteomic analysis of human bile

Osteopontin and integrin are involved in cholesterol gallstone formation

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