We read with great interest the study by Hegyi et al 1 which reported that a commonly occurring haplotype spanning the PRSS1-PRSS2 locus (encoding human cationic and anionic trypsinogens) is associated with chronic pancreatitis. While PRSS1 is the major focus in many studies,2 3 PRSS2 is also a major trypsinogen isoform synthesised in human pancreas. In normal human, the PRSS1/PRSS2 ratio is approximately 2:1.4 Chronic alcoholism increases the risk of pancreatitis. Strikingly, in these patients, total trypsinogen secretion was increased with selective upregulation of PRSS2, reversing the PRSS1/PRSS2 ratio.5 In vitro studies have shown human PRSS2 more sensitive to autocatalytic degradation and with lower autoactivation than PRSS1.6 In test tube assays under conditions of intracellular pathological trypsinogen activation, mixtures of PRSS1 and PRSS2 with increasing ratios of PRSS2 had markedly decreased rates of trypsinogen activation and yields of active trypsin.6 These observations led to a hypothesis that upregulation of PRSS2 may play a protective role against pancreatitis.6 …

中文翻译：

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人 PRSS2 转基因表达加剧小鼠胰腺炎

我们饶有兴趣地阅读了 Hegyi 等人的研究 1，该研究报道了跨越 PRSS1-PRSS2 基因座（编码人类阳离子和阴离子胰蛋白酶原）的常见单倍型与慢性胰腺炎相关。虽然 PRSS1 是许多研究的主要焦点2 3，但 PRSS2 也是人胰腺中合成的主要胰蛋白酶原亚型。在正常人中，PRSS1/PRSS2 比例约为 2:1.4 慢性酒精中毒会增加患胰腺炎的风险。引人注目的是，在这些患者中，胰蛋白酶原分泌总量随着 PRSS2 的选择性上调而增加，从而逆转了 PRSS1/PRSS2 的比例。 5 体外研究表明，人 PRSS2 对自催化降解更敏感，并且比 PRSS1 具有更低的自激活作用。 6 在以下试管测定中在细胞内病理性胰蛋白酶原激活的条件下，PRSS1 和 PRSS2 的混合物以及 PRSS2 比例的增加显着降低了胰蛋白酶原的激活率和活性胰蛋白酶的产量。 6 这些观察结果导致了一个假设，即 PRSS2 的上调可能对胰腺炎发挥保护作用。 6 ……