Glycoprotein 2 in health and disease: lifting the veil.
Glycoprotein 2 in health and disease: lifting the veil.
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DOI：
10.1186/s41021-021-00229-8
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发表时间：
2021-12-03
期刊：
影响因子：
--
通讯作者：
Kikuchi S
中科院分区：
文献类型：
--
作者：
Lin Y;Nakatochi M;Sasahira N;Ueno M;Egawa N;Adachi Y;Kikuchi S
2020年，我们在一项涉及日本人群的全基因组关联研究中发现了与胰腺癌易感性相关的糖蛋白2（GP2）变体。在GP2基因中携带错义编码变体（rs78193826）导致p.V432M取代的个体患胰腺癌的风险比没有这种变体的个体高约1.5倍。GP2表达于胰腺腺泡细胞酶原颗粒的内表面，负责消化酶的分选、储存和分泌。在神经元、激素或其他刺激下，GP2从酶原颗粒的膜上裂解，然后分泌到胰管和肠腔中。虽然GP 2的功能仍然知之甚少，但新出现的证据表明，它从胰腺腺泡细胞分泌后在胃肠道中发挥抗菌作用。受损的GP2功能可促进细菌粘附于肠粘膜。在这篇综述文章中，我们总结了GP2在健康和疾病中的作用，强调其在胃肠道中的功能，以及GP2基因的遗传变异及其与疾病易感性的关系。我们希望它与胰腺癌的强大遗传关联，加上它在胃肠道粘膜免疫中的新兴作用，将激发对GP2的新的研究兴趣，与其副尿调蛋白（UMOD）相比，GP2在过去30年中一直未得到充分研究。
In 2020, we discovered glycoprotein 2 (GP2) variants associated with pancreatic cancer susceptibility in a genome-wide association study involving the Japanese population. Individuals carrying a missense coding variant (rs78193826) in the GP2 gene resulting in a p.V432M substitution had an approximately 1.5-fold higher risk of developing pancreatic cancer than those without this variant. GP2 is expressed on the inner surface of zymogen granules in pancreatic acinar cells, which are responsible for the sorting, storage and secretion of digestive enzymes. Upon neuronal, hormonal, or other stimulation, GP2 is cleaved from the membrane of zymogen granules and then secreted into the pancreatic duct and intestinal lumen. While the functions of GP2 remain poorly understood, emerging evidence suggests that it plays an antibacterial role in the gastrointestinal tract after being secreted from pancreatic acinar cells. Impaired GP2 functions may facilitate the adhesion of bacteria to the intestinal mucosa. In this review article, we summarize the role of GP2 in health and disease, emphasizing its functions in the gastrointestinal tract, as well as genetic variations in the GP2 gene and their associations with disease susceptibility. We hope that its robust genetic associations with pancreatic cancer, coupled with its emerging role in gastrointestinal mucosal immunity, will spur renewed research interest in GP2, which has been understudied over the past 30 years compared with its paralog uromodulin (UMOD).
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DOI：
10.1038/s41575-020-00360-x
发表时间：
2021-01
期刊：
Nature reviews. Gastroenterology & hepatology
影响因子：
--
作者：
Kaplan GG;Windsor JW
通讯作者：
Windsor JW
影响因子：
13.2
作者：
Garimella, Pranav S.;Bartz, Traci M.;Sarnak, Mark J.
通讯作者：
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影响因子：
30.8
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通讯作者：
Rich, Stephen S.
影响因子：
14.8
作者：
Kumar, Prateek;Henikoff, Steven;Ng, Pauline C.
通讯作者：
Ng, Pauline C.
影响因子：
30.8
作者：
Kircher, Martin;Witten, Daniela M.;Jain, Preti;O'Roak, Brian J.;Cooper, Gregory M.;Shendure, Jay
通讯作者：
Shendure, Jay