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Interstitial matrix components in relation to the pathogenesis of fibrosis

Abstract

慢性膵炎の症例は近年増加の一途をたどっており,その発症機序と病態の解明および対策の確立が急がれている。慢性膵炎の重要な所見の一つである膵間質線維化の発生機序の解明および早期発見法の確立は重要な課題であるが,従来の知見は断片的にすぎない。そこで,筆者らは膵線維化の系統的な研究を始めるにあたって,細胞間マトリックスの構成成分と線維化に関する従来の知見および今後の課題を整理した。細胞間マトリックスのうちでも特にコラーゲン,グリコサミノグリカン,フィブロネクチンをとりあげ,その構造と機能および組織の線維化形成における役割について文献的考察を行った。今後,膵組織および膵液中のプロリンハイドロキシラーゼ,コラーゲンとその型別分布および各型コラーゲンの比,ヘキソサミン,デルマタン硫酸,フィブロネクチン,ラミニンを検討することが重要と思われた。Increasing numbers of patients with chronic pancreatitis have been reported all over the world, including Japan. Pathogenesis of chronic pancreatitis has remained to be revealed and the early detection has remaind difficult despite extensive investigations. Interstitial fibrosis forms one of the most important histopathological features of chronic pancreatitis along with loss of parenchyma and irregular dilatation of the ducts and ductules. However, only a limited numbers of reports have been pubiished on the pathogenetic mechanisms of interstitial fibrosis of the pancres, because tissue materials are not easily accessible and blood samples can hardly reflect the fibrotic process of the pancreas unlike the case of the iiver. Our Preliminary studies revealed that biochemical and immunochemical analysis of pure pancreatic juice, such as determination of collagen, hexosamine, fibronectin and proline hydroxylase, might reflect the fibrotic process of the pancreas. The results led us to review the earlier reports on inter-cellular matrix in relation to the formation of fibrosis to find suitable markers to be evaluated in the future systematic investigations. The review revealed that pure pancreatic juice should be analyzed for collagen, types of collagen, hexosamine, dermatan sulfate, fibronectin, larninin, proline hydroxylase, collagenase and cathepsin B(1)

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