Matrix glycoprotein differentially changes in liver regeneration and cirrhosis : Glycosylation alters ligand binding in matrix remodeling

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概要

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• Background Vitronectins (VN) are multifunctional adhesive glycoproteins that are present in plasma and the extracellular matrix of most tissues. We previously reported that the collagen-binding activity of VN is enhanced by a change in glycosylation in vitro and during liver regeneration after partial hepatectomy in vivo [Uchibori-Iwaki et al., Glycobiology (2000) 10, 865-874]. Plasma concentrations of VN declined in rats during liver regeneration 24 h after partial hepatectomy, while carbohydrate concentrations of VN decreased to 2/3 of that in sham-operated rats. Carbohydrate composition and lectin reactivity indicated that the N-glycan structures and sialylation significantly changed without affecting the peptide portion after partial hepatectomy. VN from partially hepatectomized rats were found to exhibit markedly enhanced binding to type I collagen. The enzymatic deglycosylation of VN demonstrated that collagen binding increased by 1.2 times after deN-glycosylation of VN, while it increased by more than 2.9 times after desialylation. To elucidate the biological significance of glycan modulation, changes of VN in cirrhosis were studied and compared with those during liver regeneration. Methods VNs purified from patients' and normal plasma were examined for plasma concentration and collagen-binding activity by ELISA, reactivity against lectins by dot blotting, and carbohydrate composition. Results Plasma concentrations of VN declined in chronic liver diseases in the order of hepatitis>cirrhosis>hepatocellular carcinoma with cirrhosis. Lectin reactivity and carbohydrate analyses of purified VN. from cirrhotic plasma (LC-VN) indicated that sialylation was elevated. LC-VN exhibited decreased binding to type I collagen. Collagen-binding studies of plasma before and after urea-treatment indicated that the active form of VN increased in cirrhotic plasma. Conclusions The attenuated collagen-binding activity of LC-VN is attributable to a change of glycosylation. The increase of active VN in cirrhotic plasma may contribute to the matrix incorporation of VN. These findings suggest that the collagen binding activity of VN is modulated by the alteration of peptide glycosylation during liver regeneration after partial hepatectomy and during the pathological processes, which may contribute to the tissue remodeling processes.

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著者

• KATO Shigemi

  Department of Biochemistry and First Department of Physiology, St. Marianna University School of Med

• AKAMATSU Nobu

  Department of Biochemistry and First Department of Physiology, St. Marianna University School of Med

• Kato Shigemi

  Department Of Biochemistry St. Marianna University School Of Medicine

• Kato Shigemi

  Department Of Biochemistry And First Department Of Physiology St. Marianna University School Of Medi

• Akamatsu Nobu

  Department Of Biochemistry St. Marianna University School Of Medicine

• Akamatsu Nobu

  Department Of Biochemistry And First Department Of Physiology St. Marianna University School Of Medi

• Ogawa Haruko

  Department Of Chemistry Faculty Of Science Ochanomizu University

• Ogawa H

  Graduate School Of Humanities And Sciences Graduate School Of Ochanomizu University

• Ogawa Haruko

  Department Of Advanced Biosciences Graduate School Of Humanities And Sciences Ochanomizu University

• Oda-tamai Sachie

  Department Of Biochemistry St. Marianna University School Of Medicine

• Suzuki Risa

  Graduate School of Humanities and Sciences, Graduate School of Ochanomizu University

• Yamada Sadako

  Department of Pathological Science and Technology, Faculty of Medicine, Tottori University

• Uchibori-Iwaki Haruhi

  Graduate School of Humanities and Sciences, Graduate School of Ochanomizu University

• Ogawa Haruko

  Graduate School of Humanities and Sciences, Graduate School of Ochanomizu University

• Suzuki Risa

  Graduate School Of Humanities And Sciences Graduate School Of Ochanomizu University

• Yamada Sadako

  Department Of Pathological Science And Technology Faculty Of Medicine Tottori University

• Uchibori-iwaki Haruhi

  Graduate School Of Humanities And Sciences Graduate School Of Ochanomizu University

• Ogawa Haruko

  Graduate School Of Humanities And Sciences Graduate School Of Ochanomizu University

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