期刊
AAPS JOURNAL
卷 21, 期 5, 页码 -出版社
SPRINGER
DOI: 10.1208/s12248-019-0359-1
关键词
ontogeny; renal transporters; liver; kidney; quantitative proteomics; paired samples
资金
- UWRAPT (University of Washington Research Affiliate Program on Transporters - Biogen)
- UWRAPT (University of Washington Research Affiliate Program on Transporters - Genentech)
- UWRAPT (University of Washington Research Affiliate Program on Transporters - Merck Co., Inc)
- UWRAPT (University of Washington Research Affiliate Program on Transporters - Gilead)
- UWRAPT (University of Washington Research Affiliate Program on Transporters - Takeda)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH grant [R01.HD081299]
- NIH [HHSN275200900011C, N01-HD-9-0011]
Renal transporters, which are primarily located in the proximal tubules, play an important role in secretion and nephrotoxicity of drugs. The goal of this study was to characterize the age-dependent protein abundance of human renal transporters. A total of 43 human kidneys, 26 of which were paired with livers from the same donors, were obtained and classified into three age groups: children (<12years), adolescents (12 to <18years), and adults (>18years). Protein abundance of kidney-specific anatomical markers, aquaporins 1 and 2 (markers of proximal and distal/collecting tubules, respectively), and 17 transporters was quantified by LC-MS/MS proteomics. Six out of 43 kidney samples were identified as outliers (Grubbs' test) that were significantly different from the others with relatively higher aquaporin 2 to aquaporin 1 ratio, indicating that these cortex samples were likely contaminated by medulla (representing distal/collecting tubules). No significant age-related changes (age>1year) were observed for renal transporter abundance, albeit OCT2 abundance was modestly higher (<50%) in adolescents than that in adults. Higher protein-protein correlation between transporters was observed in the kidney but abundance of transporters between tissues was not correlated. The use of aquaporins 1 and 2 provides a method for identifying kidney cortex with significant contamination from medulla containing distal and collecting tubules. The abundance and protein-protein correlation data can be used in physiologically based pharmacokinetic (PBPK) modeling and simulation of renal drug disposition and clearance in pediatric populations.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据