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Keywords:

  • dendritic cells;
  • epithelial-mesenchymal transitions;
  • experimental models;
  • extracellular matrix;
  • fibrosis;
  • glomerulonephritis;
  • lupus nephritis;
  • obstructive nephropathy

Summary

  1. Top of page
  2. Summary
  3. Acknowledgements
  4. References

This review series consists of seven articles, which focus on the different processes that are involved in the initiation or prevention of renal disease. The articles incorporate a critical analysis of the different experimental models that are used currently in this field of research. They provide an expert overview which is of particular relevance to glomerular diseases, renal fibrosis and obstructive kidney diseases, and all their contributions have significant implications for our understanding of human health and disease.

In the first article, Fragiadaki & Mason (2011) set out the key molecular pathways involved in potentially pro-fibrotic epithelial-mesenchymal transitions (EMT), and provide a critical analysis of the problem that EMT are readily demonstrated in vitro, yet are hard to observe reproducibly in vivo even using lineage tracing in mice.

Dussaule et al. (2011) address further the debate over the source of cells contributing to renal fibrosis and extracellular matrix accumulation, and explain authoritatively how fibrosis is reversible in a variety of in vitro and importantly also in vivo settings.

The third article, by Meran and Steadman (2011) takes us deeper into the behaviour of interstitial myofibroblasts including their modification of the extracellular matrix and the accumulation of hyaluronans that is implicated in promoting EMT. In addition they explain that the profile of cell-surface heparan sulphate proteoglycans expressed in the interstitium affects the availability and actions of growth factors such as Fibroblast Growth Factor (FGF)-2 and Transforming Growth factor (TGF)β.

Obstruction of urinary outflow experimentally in adult animals causes rapid fibrotic changes that have been studied widely. However, as Klein et al. (2011) explain comprehensively, obstruction in adult animals does not accurately reproduce the changes of congenital obstructions in humans. These authors analyse the pathological and functional changes that develop in a surprisingly wide range of models, and discuss the importance of hydrostatic, inflammation-related and other factors in obstructive nephropathies.

Hochheiser et al. (2011) explain how the renal interstitium, that supports the nephrons and vasculature, contains a rich network of dendritic cells contributing to innate immune responses as well as being master regulators of adaptive immunity. The authors summarize clearly their understanding of the role of renal dendritic cells in diverse mouse models of acute and chronic renal diseases, including unilateral ureteral obstruction (UUO).

The participation of oxidative stress in mediating fibrosis in response to UUO is the focus of the article by Dendooven et al. (2011). They review key observations assessing the roles of NOS and NADPH oxidases and consider the potential for therapeutic use offered by inhibitors.

A confounding (sometimes confusing) factor that needs to be taken into account when assessing models of renal disease is the species, and even the strain of animal being studied, as some are relatively resistant to particular renal insults. For example, inoculation with preparations of glomerular basement membrane produces experimental auto-immune glomerulonephritis (EAG) in some species that resembles the renal manifestations of human Goodpasture’s Disease, but variably in different strains. In our final article, Reynolds (2011) has expertly summarised knowledge gained over 30 years of research into such models, culminating in elegant studies that highlighted a region of rat chromosome 13 as conferring susceptibility to EAG, and identified candidate genes at this locus.

Acknowledgements

  1. Top of page
  2. Summary
  3. Acknowledgements
  4. References

I am grateful to The International Journal of Experimental Pathology for financial support to attend the 21st European Renal Cell Study Group meeting, and would like to thank the ERCSG (http://www.ercsg.org) for its stimulating series of scientific meetings that introduced me to many excellent renal researchers including contributors to this special issue.

References

  1. Top of page
  2. Summary
  3. Acknowledgements
  4. References