Cell models for studying renal physiology

Abstract

The development over the past 20 years of a variety of cultured renal tubule cell lines derived from different parts of the renal tubule has provided invaluable powerful cell systems for in vitro analyses of the various tubule segment-specific biochemical functions and ion transport processes. Immortalized cell lines have been established using different hybrid gene constructs, most of them carrying the immortalizing simian virus 40 large T antigen (Tag) gene. The development of transgenic mice carrying unregulated Tag, and of others in which the expression of Tag remains controlled, has made it possible to establish permanent cell lines derived from microdissected or immunoselected renal proximal, distal, and collecting duct tubules. This review summarizes the different strategies of cellular immortalization used and the most frequently used human, rabbit, rat, and mouse tubule cell lines. This review provides an overview of the use of immortalized mouse tubule cell lines for in vitro analyses of various tubule cell-specific functions and the regulation of ion transporters and membranous channels. The advantages of using primary cultures of isolated tubules dissected from physiopathological models of transgenic mice are also discussed.

Key to Opening Kidney for In Vitro–In Vivo Extrapolation Entrance in Health and Disease: Part I: In Vitro Systems and Physiological Data

“…http:// www.lgcstandards-atcc.org/), and can be generally useful for investigating renal tubule function and toxicity in vitro (41)(42)(43)(44). For example ci-PTEC cells were used to investigate the impact of CYP3A5 and P-glycoprotein (P-gp/MDR1, ABCB1) genetic variation on tacrolimus metabolism, which could allow mechanistic insights into nephrotoxicity associated with this calcineurin inhibitor (44).…”

Quantitative estimation of transmembrane ion transport in rat renal collecting duct principal cells

“…Since investigations of these cells in vivo are difficult due to the complexity of the intact medulla, research is generally focused on in vitro studies of cells in culture and excised fragments of collecting ducts (Burg 1972;Bens and Vandewalle 2008). Fluorescent microscopy and specific fluorescent molecular probes allowing the measurement of intracellular concentration of a wide spectrum of ions are among the most promising experimental techniques for studying cells in vitro (Meuwis et al 1995;Despa et al 2000;Jayaraman and Verkman 2000).…”

Gene set enrichment analysis and ingenuity pathway analysis of metastatic clear cell renal cell carcinoma cell line

“…Caki-1 cells represent a suitable in vitro model for studying the human proximal tubule epithelium and mRCC (26,29). This cell line was compared with human kidney epithelial cells (ASE-5063), which is an ideal cell line for studying the development and biochemical function of the kidneys (3,14). Differentially expressed gene profiling data of the above cell lines were further analyzed using Ingenuity Pathway Analysis (IPA) software to interpret the biological changes, altered canonical pathways, upstream transcriptional regulators, and gene networks of the metastatic Caki-1 cell line.…”