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新型条件永生化人近端肾小管细胞系表达功能转运体。

Novel conditionally immortalized human proximal tubule cell line expressing functional influx and efflux transporters.

机构信息

Laboratory of Pediatrics and Neurology (656), Radboud University Nijmegen Medical Center, P.O. 9101, 6500 HB, Nijmegen, The Netherlands.

出版信息

Cell Tissue Res. 2010 Feb;339(2):449-57. doi: 10.1007/s00441-009-0882-y. Epub 2009 Nov 10.

DOI:10.1007/s00441-009-0882-y
PMID:19902259
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2817082/
Abstract

Reabsorption of filtered solutes from the glomerular filtrate and excretion of waste products and xenobiotics are the main functions of the renal proximal tubular (PT) epithelium. A human PT cell line expressing a range of functional transporters would help to augment current knowledge in renal physiology and pharmacology. We have established and characterized a conditionally immortalized PT epithelial cell line (ciPTEC) obtained by transfecting and subcloning cells exfoliated in the urine of a healthy volunteer. The PT origin of this line has been confirmed morphologically and by the expression of aminopeptidase N, zona occludens 1, aquaporin 1, dipeptidyl peptidase IV and multidrug resistance protein 4 together with alkaline phosphatase activity. ciPTEC assembles in a tight monolayer with limited diffusion of inulin-fluorescein-isothiocyanate. Concentration and time-dependent reabsorption of albumin via endocytosis has been demonstrated, together with sodium-dependent phosphate uptake. The expression and activity of apical efflux transporter p-glycoprotein and of baso-lateral influx transporter organic cation transporter 2 have been shown in ciPTEC. This established human ciPTEC expressing multiple endogenous organic ion transporters mimicking renal reabsorption and excretion represents a powerful tool for future in vitro transport studies in pharmacology and physiology.

摘要

从肾小球滤液中重吸收滤过的溶质和排泄废物和外源性物质是肾近端小管 (PT) 上皮的主要功能。表达一系列功能转运蛋白的人 PT 细胞系将有助于增强目前对肾脏生理学和药理学的认识。我们通过转染和亚克隆从健康志愿者尿液中脱落的细胞，建立并鉴定了一种条件永生化的 PT 上皮细胞系 (ciPTEC)。该细胞系的 PT 来源已通过形态学和表达氨基肽酶 N、闭合蛋白 1、水通道蛋白 1、二肽基肽酶 IV 和多药耐药蛋白 4 以及碱性磷酸酶活性得到证实。ciPTEC 以紧密的单层组装，对荧光素-异硫氰酸菊酯的通透性有限。已经证明白蛋白通过内吞作用进行浓度和时间依赖性重吸收，同时还进行钠依赖性磷酸盐摄取。ciPTEC 中表达和活性的顶端外排转运蛋白 P-糖蛋白和基底外侧内流转运蛋白有机阳离子转运蛋白 2。这种建立的表达多种内源性有机离子转运蛋白的人 ciPTEC 模拟肾脏重吸收和排泄，代表了未来在药理学和生理学中进行体外转运研究的有力工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a26/2817082/3d08d37b716b/441_2009_882_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a26/2817082/281ee44d3107/441_2009_882_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a26/2817082/27fdd6228f51/441_2009_882_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a26/2817082/6027316d21a3/441_2009_882_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a26/2817082/6b03fe535a64/441_2009_882_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a26/2817082/3d08d37b716b/441_2009_882_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a26/2817082/281ee44d3107/441_2009_882_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a26/2817082/40c70293f9ec/441_2009_882_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a26/2817082/ad829212e773/441_2009_882_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a26/2817082/49e627bf9cac/441_2009_882_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a26/2817082/27fdd6228f51/441_2009_882_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a26/2817082/6027316d21a3/441_2009_882_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a26/2817082/6b03fe535a64/441_2009_882_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a26/2817082/3d08d37b716b/441_2009_882_Fig8_HTML.jpg

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