Global expression of molecular transporters in the human vaginal tract: implications for HIV chemoprophylaxis.
Global expression of molecular transporters in the human vaginal tract: implications for HIV chemoprophylaxis.
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DOI：
10.1371/journal.pone.0077340
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Baum MM
中科院分区：
文献类型：
--
作者：
Gunawardana M;Mullen M;Moss JA;Pyles RB;Nusbaum RJ;Patel J;Vincent KL;Wang C;Guo C;Yuan YC;Warden CD;Baum MM
使用抗逆转录病毒药物进行暴露前化学预防（PrECP）是预防女性艾滋病毒性传播的一种有前途的策略。人类阴道（VT）中的分子转运蛋白可能在确定药物处置以及因此的药效学结果方面发挥关键作用。然而，人们对这些转运蛋白在阴道组织中的表达知之甚少，这是一个关键的知识差距。我们的研究分析了 6 名接受妇科手术的育龄妇女的 44 个阴道组织样本的全基因组转录组。分析显示，出乎意料的是，大量（43%）与膜转运蛋白相对应的基因亚型在所有样本中过度表达（高于中值表达水平）。鉴定出 12 个高表达膜转运蛋白的子集，其中包含溶质载体超家族的 10 个成员 (83%)。在不同受试者之间观察到膜转运蛋白基因表达的最大差异，但沿着 VT 的前后轴也发现了更细微的差异表达。微阵列分析与 RT-qPCR 测量的交叉验证证明了这些数据集之间的高度一致性。阴道组织中膜转运蛋白的免疫荧光标记高度依赖于组织/细胞类型。目前正在评估的抗逆转录病毒 PrECP 药物是分子转运蛋白的底物，这些分子转运蛋白普遍表达，但在所有样本中都属于表达过度或表达不足的类别，这表明载体介导的过程在确定这些异生物质在阴道组织中的处置中发挥着复杂的作用。这些发现对于成功开发用于女性控制的 HIV PrECP 的口服或阴道内产品具有重要意义。
Pre-exposure chemoprophylaxis (PrECP) using antiretroviral agents is a promising strategy for the prevention of sexual HIV transmission in women. Molecular transporters in the human vaginal tract (VT) may play a pivotal role in determining drug disposition and, consequently, pharmacodynamic outcomes in these efforts. Little is known, however, on the expression of these transporters in vaginal tissues, representing a critical knowledge gap. Our study analyzed the genome-wide transcriptome in 44 vaginal tissue samples from 6 reproductive-age women undergoing gynecologic surgeries. The analysis revealed that, unexpectedly, a large number (43%) of gene isoforms corresponding to membrane transporters were over-expressed (above the median expression level) in all samples. A subset of 12 highly expressed membrane transporters was identified and contained 10 members (83%) of the solute carrier superfamily. The largest difference in membrane transporter gene expression was observed across subjects, but more subtle differential expression also was found along the anterior-posterior axis of the VT. Cross-validation of the microarray analyses with measurements RT-qPCR demonstrated high concordance between these data sets. Immunofluorescence labeling of membrane transporter proteins in vaginal tissues was highly dependent on tissue/cell types. Antiretroviral PrECP drugs currently under evaluation are substrates for molecular transporters that were commonly expressed, but fell into both over- or under-expressed categories in all samples, suggesting a complex role for carrier-mediated processes in determining the disposition of these xenobiotics in vaginal tissues. These findings hold important implications for the successful development of products, either oral or intravaginal, for female-controlled HIV PrECP.
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影响因子：
2.3
作者：
Janoria, Kumar G.;Boddu, Sai H. S.;Mitra, Ashim K.
通讯作者：
Mitra, Ashim K.
影响因子：
2
作者：
Anand, BS;Katragadda, S;Mitra, AK
通讯作者：
Mitra, AK
影响因子：
5.8
作者：
Jain, R;Agarwal, S;Mitra, AK
通讯作者：
Mitra, AK
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
5.2
作者：
Ford, J;Khoo, SH;Back, DJ
通讯作者：
Back, DJ