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Pancreatic elastases

胰腺弹性蛋白酶

基本信息

批准号：
8437036
负责人：
Miklos Sahin-Toth
金额：
$ 35.6万
依托单位：
BOSTON UNIVERSITY MEDICAL CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-01-01 至 2016-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8437036
关键词：
Acinar Cell Address Adenoviruses Advanced Development Affect Apoptotic Applications Grants Back Cattle Cell Death Collaborations Communities Complex Confusion Data Digestion Disease Elastases Enzyme Precursors Enzymes Exhibits Genes Genomics Germany Human Inflammatory Isoenzymes Measures Mediating Messenger RNA Methodology Methods Molecular Chaperones Mus Mutation Orthologous Gene Pancreas Pancreatic Elastase Pancreatitis Pathway interactions Patients Peptide Hydrolases Peptide Initiation Factors Peptides Phage Display Phosphorylation Physiological Physiology Protein Isoforms Publishing RNA Splicing Rattus Reporting Research Design Risk Risk Factors Role Ruminants Substrate Specificity Susceptibility Gene Technology Time Transfection Trypsinogen Up-Regulation Variant calreticulin chronic pancreatitis chymotrypsinogen C design endoplasmic reticulum stress inhibitor/antagonist insight meetings mutant novel novel diagnostics novel therapeutic intervention public health relevance research study species difference transcription factor CHOP

项目摘要

DESCRIPTION (provided by applicant): The objectives of the present grant proposal are to characterize the physiological functions of pancreatic elastases and to investigate the mechanism by which elastase mutants act as risk factors for chronic pancreatitis in humans. This grant application is intended to meet a growing need in the pancreas community for the understanding of elastase function both in pancreatic physiology and disease. In humans, there are five pancreatic elastase genes (ELA1, ELA2A, ELA2B, ELA3A, and ELA3B) which give rise to three functional elastases (ELA2A, ELA3A and ELA3B). In the mouse ELA1, ELA2A and ELA3B seem to be expressed. The specific aims studied are designed to address (i) the substrate specificity of human and mouse elastases; (ii) complex formation between proelastases and other pancreatic proteases; and (iii) the functional consequences of proelastase mutations identified in subjects with chronic pancreatitis.

描述（由申请人提供）：本资助提案的目的是描述胰腺弹性蛋白酶的生理功能，并研究弹性蛋白酶突变体作为人类慢性胰腺炎危险因素的机制。这项拨款申请旨在满足胰腺社区日益增长的需求，以了解弹性蛋白酶在胰腺生理学和疾病中的功能。在人类中，存在五种胰腺弹性蛋白酶基因（ELA 1、ELA 2A、ELA 2B、ELA 3A和ELA 3B），其产生三种功能性弹性蛋白酶（ELA 2A、ELA 3A和ELA 3B）。在小鼠中，似乎表达ELA 1、ELA 2A和ELA 3B。研究的具体目的旨在解决（i）人和小鼠弹性蛋白酶的底物特异性;（ii）弹性蛋白酶原和其他胰腺蛋白酶之间的复合物形成;以及（iii）在慢性胰腺炎受试者中鉴定的弹性蛋白酶原突变的功能后果。