Excess Secretion of Gel-Forming Mucins and Associated Innate Defense Proteins with Defective Mucin Un-Packaging Underpin Gallbladder Mucocele Formation in Dogs.
Excess Secretion of Gel-Forming Mucins and Associated Innate Defense Proteins with Defective Mucin Un-Packaging Underpin Gallbladder Mucocele Formation in Dogs.
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DOI：
10.1371/journal.pone.0138988
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Gookin JL
中科院分区：
文献类型：
--
作者：
Kesimer M;Cullen J;Cao R;Radicioni G;Mathews KG;Seiler G;Gookin JL
粘液保护胆囊是至关重要的，但我们知道很少有关的机制。在家犬中，称为胆囊粘液囊肿形成的紧急综合征的特征是异常粘液的过度分泌，导致胆囊阻塞和破裂。胆囊粘液囊肿形成的原因尚不清楚。在这种疾病的这些第一个机制研究中，我们研究了正常和形成粘液囊的狗胆囊，以确定罪魁祸首粘蛋白的来源、身份、生物物理特性和蛋白质缔合物，目的是确定异常粘液行为的原因。我们确定粘液囊肿的形成涉及胆囊上皮细胞过继性过度分泌具有异常性质的凝胶形成粘蛋白。粘液的特征在于Muc5ac相对于Muc5b的预防性显著增加、有缺陷的粘蛋白解包装和能够显著改变粘液的物理和功能性质的粘蛋白相互作用的先天防御蛋白。这些发现为异常粘液行为提供了解释，并基于与囊性纤维化患者气道中观察到的粘液的相似性，表明维持胆囊上皮水合作用的异常机制可能是犬粘液囊肿形成的诱发因素。
Mucosal protection of the gallbladder is vital yet we know very little about the mechanisms involved. In domestic dogs, an emergent syndrome referred to as gallbladder mucocele formation is characterized by excessive secretion of abnormal mucus that results in obstruction and rupture of the gallbladder. The cause of gallbladder mucocele formation is unknown. In these first mechanistic studies of this disease, we investigated normal and mucocele-forming dog gallbladders to determine the source, identity, biophysical properties, and protein associates of the culprit mucins with aim to identify causes for abnormal mucus behavior. We established that mucocele formation involves an adoptive excess secretion of gel forming mucins with abnormal properties by the gallbladder epithelium. The mucus is characterized by a disproportionally significant increase in Muc5ac relative to Muc5b, defective mucin un-packaging, and mucin-interacting innate defense proteins that are capable of dramatically altering the physical and functional properties of mucus. These findings provide an explanation for abnormal mucus behavior and based on similarity to mucus observed in the airways of people with cystic fibrosis, suggest that abnormal mechanisms for maintenance of gallbladder epithelial hydration may be an instigating factor for mucocele formation in dogs.