胰腺炎的遗传背景。
Genetic background of pancreatitis.
作者信息
Hirota Masahiko, Ohmuraya Masaki, Baba Hideo
机构信息
Department of Gastroenterological Surgery, Kumamoto University Graduate School of Medical Sciences, Honjo, Kumamoto-City, Kumamoto 860-0811, Japan.
出版信息
Postgrad Med J. 2006 Dec;82(974):775-8. doi: 10.1136/pgmj.2006.050591.
Abstract
Trypsin activity is properly suppressed by pancreatic secretory trypsin inhibitor (PSTI), which is also known as serine protease inhibitor Kazal type 1 (SPINK1), thereby preventing damage to pancreatic acinar cells as a first line of defence. However, if trypsin activation exceeds the capacity of PSTI/SPINK1, a subsequent cascade of events leads to the activation of various proteases that damage cells. Five mutations (R122H, N29I, A16V, D22G and K23R) in cationic trypsinogen and two mutations (N34S and M1T) in the PSTI/SPINK1 gene have been found to correlate significantly with the onset of pancreatitis. From analyses of hereditary pancreatitis and the phenotype of PSTI/SPINK1 (Spink3) knockout mice, we showed that the imbalance of trypsin activation and its inhibition by PSTI/SPINK1 would lead to the development of pancreatitis.
摘要
胰蛋白酶活性受到胰腺分泌性胰蛋白酶抑制剂（PSTI，也称为Kazal型1丝氨酸蛋白酶抑制剂，即SPINK1）的适当抑制，从而作为第一道防线防止胰腺腺泡细胞受损。然而，如果胰蛋白酶的激活超过了PSTI/SPINK1的抑制能力，随后一系列事件会导致各种蛋白酶激活，进而损伤细胞。已发现阳离子胰蛋白酶原中的五个突变（R122H、N29I、A16V、D22G和K23R）以及PSTI/SPINK1基因中的两个突变（N34S和M1T）与胰腺炎的发病显著相关。通过对遗传性胰腺炎和PSTI/SPINK1（Spink3）基因敲除小鼠表型的分析，我们发现胰蛋白酶激活与PSTI/SPINK1对其抑制作用的失衡会导致胰腺炎的发生。
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