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Involvement of osteopontin as a core protein in cholesterol gallstone formation

  • Original article
  • Published:
Journal of Hepato-Biliary-Pancreatic Surgery

Abstract

Background and purpose

Matrix proteins are considered to be essential for biomineralization and to be important factors in the formation and growth of gallstones. Osteopontin (Opn) is a noncollagenous, acidic bone-matrix glycoprotein, which is sialated and phosphorylated and which has a cell-binding peptide sequence of glycine–arginine–glycine–aspartate–serine (GRGDS). To investigate the role of Opn in cholesterol gallstone formation, we have studied the involvement of Opn in cholesterol gallstone formation in the human gallbladder wall, in the stones, and in the mouse gallbladder using a gallstone experimental model.

Methods

Immunohistochemical staining was used in the human gallbladder wall and human gallstones and the determination of mRNA expression by reverse transcriptase-PCR was used in the mouse gallbladder of a gallstone experimental model.

Results

The epithelium of stone-laden gallbladders demonstrated high Opn reactivity, as did the core of the stones. Microscopically detected early stones without macroscopic evidence of lithiasis showed the same immunoreactivity as larger stones. Stone-laden gallbladders were infiltrated by macrophages showing intense Opn expression. In gallstone-forming mice, the expression of Opn mRNA and its protein were significantly increased in the gallbladder wall in the early phase of a lithogenic diet intake, before the initiation of inflammation.

Conclusion

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

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Acknowledgments

The authors thank Mrs. Fusako Kamata, Dr. Fumiharu Akai, Dr. Takao Satou, Dr. Tatuki Itoh, and Dr. Michio Kato of our University for their kind help in the realization of this collaboration study.

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Authors and Affiliations

  1. Department of Surgery, School of Medicine, Kinki University, 377-2 Ohnohigashi, Osaka-Sayama, Osaka, 589-0014, Japan

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

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  1. Hideaki Ichikawa
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  2. Motohiro Imano
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  3. Yoshifumi Takeyama
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  4. Hitoshi Shiozaki
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  5. Harumasa Ohyanagi
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Correspondence to Motohiro Imano.

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Ichikawa, H., Imano, M., Takeyama, Y. et al. Involvement of osteopontin as a core protein in cholesterol gallstone formation. J Hepatobiliary Pancreat Surg 16, 197–203 (2009). https://doi.org/10.1007/s00534-009-0043-4

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  • DOI: https://doi.org/10.1007/s00534-009-0043-4

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