Renal proximal tubular cells in suspension or in primary culture as in vitro models to study nephrotoxicity

Boogaard, Peter J.; Nagelkerke, J. Fred; Mulder, Gerard J.

doi:10.1016/0009-2797(90)90096-6

Cited by 49 publications

(23 citation statements)

References 178 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is now clear that the macrophage influx into the renal corticointerstitium is associated with progressive renal scarring in a wide range of disease states (31,32). We recently described a novel mechanism by which mononuclear leukocytes via their cell surface CD44 bind to pericellular HA cable-like structures on proximal tubular epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

Bone Morphogenic Protein-7 Inhibits Monocyte-Stimulated TGF-β1 Generation in Renal Proximal Tubular Epithelial Cells

Zhang¹,

Selbi²,

Motte³

et al. 2005

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Bone Morphogenic Protein-7 Inhibits Monocyte-Stimulated TGF-β1 Generation in Renal Proximal Tubular Epithelial Cells

Zhang¹,

Selbi²,

Motte³

et al. 2005

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

show abstract

“…Despite the various drawbacks inherent to in vitro models, human and animal immortalized renal epithelial cell lines and primary cultures of RPTC have provided useful models for research into the mechanisms of proximal tubular cell injury and death associated with ARF (Boogaard et al, 1990;Racusen, 1994;Molitoris et al, 2000). In addition, immortalized renal epithelial cell lines are good for overexpression and knockout experiments.…”

Section: In Vitro Models For Studying Rptc Repairmentioning

confidence: 99%

“…To date, the closest representations of the ideal in vitro model system are primary cultures of RPTC. Over the years, researchers have prepared primary cultures of rat, mouse, rabbit, dog, and human RPTC using a variety of isolation methods with varying degrees of success (Boogaard et al, 1990). More recently, a number of improvements have been made in primary cultures of RPTC from numerous species, including humans, that result in greater retention of the renal physiology and differentiated functions found in vivo (Kruidering et al, 1996;Gstraunthaler et al, 1999;Sens et al, 1999).…”

Section: In Vitro Models For Studying Rptc Repairmentioning

confidence: 99%

Mechanisms of Renal Cell Repair and Regeneration after Acute Renal Failure

Nony

Schnellmann²

2002

J Pharmacol Exp Ther

154

118

View full text Add to dashboard Cite

In many cases, acute renal failure (ARF) is the result of proximal tubular cell injury and death and can arise in a variety of clinical situations, especially following renal ischemia and drug or toxicant exposure. Although much research has focused on the cellular events leading to ARF, less emphasis has been placed on the mechanisms of renal cell repair and regeneration, although ARF is reversed in over half of those who acquire it. Studies using in vivo and in vitro models have demonstrated the importance of proliferation, migration, and repair of physiological functions of injured renal proximal tubular cells (RPTC) in the reversal of ARF. Growth factors have been shown to produce migration and proliferation of injured RPTC, although the specific mechanisms through which growth factors promote renal regeneration in vivo are unclear. Recently, interactions between integrins and extracellular matrix proteins such as collagen IV were shown to promote the repair of physiological functions in injured RPTC. Specifically, collagen IV synthesis and deposition following cellular injury restored integrin polarity and promoted repair of mitochondrial function and active Na ϩ transport. Furthermore, exogenous collagen IV, but not collagen I, fibronectin, or laminin, promoted the repair of physiological functions without stimulating proliferation. These findings suggest the importance of establishing and/or maintaining collagen IV-integrin interactions in the stimulation of repair of physiological functions following sublethal cellular injury. Furthermore, the pathway that stimulates repair is distinct from that of proliferation and migration and may be a viable target for pharmacological intervention.Most cases of acute renal failure (ARF) result from renal ischemia, acute drug, or toxicant exposure, affecting up to 5% of all long-term hospital patients. Despite the advent of dialysis and increasing knowledge regarding the causes and effects of ARF, nearly half of those who develop the disease do not survive, a trend that has not changed for several decades (Thadhani et al., 1996;Molitoris et al., 2000). A vast majority of research in the field of ARF has focused on the determination of events and factors that cause renal proximal tubular cell (RPTC) injury and death leading to the development of ARF. Unfortunately, the development of therapeutic strategies that are efficacious in humans with ARF has proven problematic. This suggests that the development of more successful therapies requires approaching the problem from a different vantage point (Molitoris et al., 2000). The regenerative capacity of the kidney is well documented, and more than half of noncritically ill patients who acquire ARF survive (Toback et al., 1993;Abbate and Remuzzi, 1996;Liano and Pascual, 1998). The responses of surviving RPTC are thought to be crucial to the restoration of renal function following ARF. Consequently, understanding RPTC repair and regeneration mechanisms may uncover new therapeutic targets that promote renal recovery an...

show abstract

“…Despite this difficulty, primary cultures of proximal nephron epithelium from various species have been developed, i.e., mouse (35), rat (36,37), rabbit (38), and pig (39). Although cells in primary culture tend to dedifferentiate within hours, the characteristics of those cells are usually closer to the in vivo situation as compared to cell lines.…”

Section: Higher Order Systemsmentioning

confidence: 99%

Nephrotoxicity Testing in Vitro: What We Know and What We Need to Know

Pfaller¹,

Gstraunthaler²

1998

Environmental Health Perspectives

View full text Add to dashboard Cite

The kidney is affected by many chemicals. Some of the chemicals may even contribute to endstage renal disease and thus contribute considerably to health care costs. Because of the large functional reserve of the kidney, which masks signs of dysfunction, early diagnosis of renal disease is often difficult. Although numerous studies aimed at understanding the mechanisms underlying chemicals and drugs that target various renal cell types have delivered enough understanding for a reasonable risk assessment, there is still an urgent need to better understand the mechanisms leading to renal cell injury and organ dysfunction. The increasing use of in vitro techniques using isolated renal cells, nephron fragments, or cell cultures derived from specific renal cell types has improved our insight into the molecular mechanisms involved in nephrotoxicity. A short overview is given on the various in vitro systems currently used to clarify mechanistic aspects leading to sublethal or lethal injury of the functionally most important nephron epithelial cells derived from various species. Whereas freshly isolated cells and nephron fragments appear to represent a sufficient basis to study acute effects (hours) of nephrotoxins, e.g., on cell metabolism, primary cultures of these cells are more appropriate to study long-term effects. In contrast to isolated cells and fragments, however, primary cultures tend to first lose several of their in vivo metabolic properties during culture, and second to have only a limited life span (days to weeks). Moreover, establishing such primary cultures is a time-consuming and laborious procedure. For that reason many studies have been carried out on renal cell lines, which are easy to cultivate in large quantities and which have an unlimited life span. Unfortunately, none of the lines display a state of differentiation comparable to that of freshly isolated cells or their primary cultures. Most often they lack expression of key functions (e.g., gluconeogenesis or organic anion transport) of their in vivo correspondents. Therefore, the use of cell lines for assessment of nephrotoxic mechanisms will be limited to those functions the lines express. Upcoming molecular biology approaches such as the transduction of immortalizing genes into primary cultures and the utilization of cells from transgenic animals may in the near future result in the availability of highly differentiated renal cells with markedly extended life spans and near in vivo characteristics that may facilitate the use of renal cell culture for routine screening of nephrotoxins. -Environ Health Perspect 1 06(Suppl 2):559-569 (1998). http://ehpnetl.niehs.nih.gov/docs/1998/Suppl-2/ 559-569pfaller/abstract.html

show abstract

Renal proximal tubular cells in suspension or in primary culture as in vitro models to study nephrotoxicity

Cited by 49 publications

References 178 publications

Bone Morphogenic Protein-7 Inhibits Monocyte-Stimulated TGF-β1 Generation in Renal Proximal Tubular Epithelial Cells

Bone Morphogenic Protein-7 Inhibits Monocyte-Stimulated TGF-β1 Generation in Renal Proximal Tubular Epithelial Cells

Mechanisms of Renal Cell Repair and Regeneration after Acute Renal Failure

Nephrotoxicity Testing in Vitro: What We Know and What We Need to Know

Contact Info

Product

Resources

About