Apical Membrane Alterations in Non-intestinal Organs in Microvillus Inclusion Disease.
Apical Membrane Alterations in Non-intestinal Organs in Microvillus Inclusion Disease.
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DOI：
10.1007/s10620-017-4867-5
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发表时间：
2018-03
影响因子：
3.1
通讯作者：
Shub MD
中科院分区：
文献类型：
--
作者：
Schlegel C;Weis VG;Knowles BC;Lapierre LA;Martin MG;Dickman P;Goldenring JR;Shub MD
微绒毛包涵体病（MVID）是一种严重的新生儿腹泻，主要由MYO 5 B突变引起。MYO 5 B的失活突变导致小肠中肠细胞的去极化，这引起慢性、持续的分泌性腹泻。虽然MVID患者的小肠病理学已得到很好的描述，但对MYO 5 B突变的肠外效应知之甚少。我们检查了Navajo MVID患者的胃、肝脏、胰腺、结肠和肾脏，这些患者共享单个纯合子MYO 5 B-P660 L（1979 C> TP.Pro660Leu，外显子16）。对切片进行顶膜标记物染色，以评估极化运输。Navajo MVID患者胃壁细胞中含H/K-ATP酶的管状囊泡结构发生显著变化。结肠粘膜形态正常，但在顶端埃兹蛋白和突触融合蛋白3中显示损失。MVID患者的肝细胞显示出基本转运蛋白MRP 2和BSEP的异常小管表达。胰腺显示小碎片胰岛和胰管中顶端ezrin减少。肾脏显示正常的初级纤毛。这些发现表明，Navajo MVID患者MYO 5 B中P660 L突变的影响不仅限于小肠，而且某些组织可能能够在功能上补偿顶端运输的改变。
Microvillus Inclusion Disease (MVID) is a severe form of neonatal diarrhea, caused mainly by mutations in MYO5B. Inactivating mutations in MYO5B causes depolarization of enterocytes in the small intestine, which gives rise to chronic, unremitting secretory diarrhea. While the pathology of the small intestine in MVID patients is well described, little is known about extraintestinal effects of MYO5B mutation. We examined stomach, liver, pancreas, colon and kidney in Navajo MVID patients, who share a single homozygous MYO5B-P660L (1979C>T p.Pro660Leu, exon 16). Sections were stained for markers of the apical membrane to assess polarized trafficking. Navajo MVID patients showed notable changes in H/K-ATPase-containing tubulovesicle structure in the stomach parietal cells. Colonic mucosa was morphologically normal, but did show losses in apical ezrin and Syntaxin 3. Hepatocytes in the MVID patients displayed aberrant canalicular expression of the essential transporters MRP2 and BSEP. The pancreas showed small fragmented islets and a decrease in apical ezrin in pancreatic ducts. Kidney showed normal primary cilia. These findings indicate that the effects of the P660L mutation in MYO5B in Navajo MVID patients are not limited to the small intestine, but that certain tissues may be able to compensate functionally for alterations in apical trafficking.
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影响因子：
4.8
作者：
Roland, Joseph T.;Lapierre, Lynne A.;Goldenring, James R.
通讯作者：
Goldenring, James R.
影响因子：
11.4
作者：
HANZEL, D;REGGIO, H;MANGEAT, P
通讯作者：
MANGEAT, P
影响因子：
3.3
作者：
Lapierre, LA;Kumar, R;Goldenring, JR
通讯作者：
Goldenring, JR
DOI：
10.1152/ajpcell.2001.281.2.c407
发表时间：
2001-08-01
影响因子：
5.5
作者：
Ammar, DA;Nguyen, PNB;Forte, JG
通讯作者：
Forte, JG
影响因子：
64.8
作者：
Sato, Takashi;Mushiake, Sotaro;Harada, Akihiro
通讯作者：
Harada, Akihiro