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Genetic background of pancreatitis.

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.

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  • Authors+Show Affiliations

    ,

    Department of Gastroenterological Surgery, Kumamoto University Graduate School of Medical Sciences, Honjo, Kumamoto-City, Kumamoto 860-0811, Japan. hdobaba@kaiju.medic.kumamoto-u.ac.jp

    ,

    Source

    Postgraduate medical journal 82:974 2006 Dec pg 775-8

    MeSH

    Animals
    Carrier Proteins
    Cystic Fibrosis Transmembrane Conductance Regulator
    Humans
    Mice
    Mutation
    Pancreatitis
    Trypsin Inhibitor, Kazal Pancreatic
    Trypsinogen

    Pub Type(s)

    Journal Article
    Review

    Language

    eng

    PubMed ID

    17148697

    Citation

    Hirota, Masahiko, et al. "Genetic Background of Pancreatitis." Postgraduate Medical Journal, vol. 82, no. 974, 2006, pp. 775-8.
    Hirota M, Ohmuraya M, Baba H. Genetic background of pancreatitis. Postgrad Med J. 2006;82(974):775-8.
    Hirota, M., Ohmuraya, M., & Baba, H. (2006). Genetic background of pancreatitis. Postgraduate Medical Journal, 82(974), pp. 775-8.
    Hirota M, Ohmuraya M, Baba H. Genetic Background of Pancreatitis. Postgrad Med J. 2006;82(974):775-8. PubMed PMID: 17148697.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Genetic background of pancreatitis. AU - Hirota,Masahiko, AU - Ohmuraya,Masaki, AU - Baba,Hideo, PY - 2006/12/7/pubmed PY - 2007/3/28/medline PY - 2006/12/7/entrez SP - 775 EP - 8 JF - Postgraduate medical journal JO - Postgrad Med J VL - 82 IS - 974 N2 - 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. SN - 1469-0756 UR - https://www.unboundmedicine.com/medline/citation/17148697/full_citation L2 - http://pmj.bmj.com/cgi/pmidlookup?view=long&pmid=17148697 DB - PRIME DP - Unbound Medicine ER -