Increased fluid secretion after adenoviral-mediated transfer of the aquaporin-1 cDNA to irradiated rat salivary glands

Increased fluid secretion after adenoviral-mediated transfer of the aquaporin-1 cDNA to irradiated rat salivary glands
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DOI:
10.1073/pnas.94.7.3268
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发表时间:
1997-04-01
影响因子:
11.1
通讯作者:
Baum, BJ
Baum, BJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Delporte, C;OConnell, BC;Baum, BJ

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构建了一种编码人水通道蛋白1(humanaquaporin-1,hAQP 1)的复制缺陷型重组腺病毒AdhAQP 1,该病毒可在多种上皮细胞系中表达。在极化的MDCK细胞单层中,hAQP 1定位于上皮和基底侧质膜,AdhAQP 1感染的单层对渗透压梯度的反应是未感染的单层或对照病毒感染的单层的4倍。Western印迹分析显示,在粗质膜中hAQP 1表达显著,免疫组化染色显示腺泡和导管细胞中hAQP 1表达显著。在单次照射(17.5或21戈伊)后3或4个月,AdhAQP 1对大鼠下颌下腺的作用是对照组的2 - 3倍。这些结果表明,hAQP 1基因转移可能是治疗照射后唾液功能减退的一种独特方法。
A replication-deficient, recombinant adenovirus encoding human aquaporin-1 (hAQP1), the archetypal water channel, was constructed, This virus, AdhAQP1, directed hAQP1 expression in several epithelial fell lines in vitro. In polarized MDCK cell monolayers, hAQP1 was localized in the epical and basolateral plasma membranes, Fluid movement across monolayers infected by AdhAQP1 in response to an osmotic gradient was approximate to 4-fold that seen with uninfected monolayers or monolayers infected by a control virus, When AdhAQP1 was administered to rat submandibular glands by retrograde ductal instillation, significant hAQP1 expression was observed by Western blot analysis in crude plasma membranes and by immunohistochemical staining in both acinar and ductal cells. Three or four months after exposure to a single radiation dose (17.5 or 21 Gy, respectively), AdhAQP1 administration to rat submandibular glands led to a two- to threefold increase in salivary secretion compared with secretion from glands administered a control virus, These results suggest that hAQP1 gene transfer may have potential as an unique approach For the treatment of postradiation salivary hypofunction.