Mapping the kidney glomerulus

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Despite the fact that kidney diseases cause great suffering and put considerable strain on hospital resources, far too little is known about their causes. Researchers at Karolinska Institutet and Uppsala University are now able to join forces to identify the underlying causes at a molecular level.

Diseases of the kidney glomerulus, the bundle of blood capillaries that help to filter the blood, are responsible for two-thirds of the cases of severe kidney disease that ultimately require prolonged dialysis or transplantation. Despite this, the general understanding of the molecular mechanisms of those diseases is still very limited and specific drugs do not exist.

A comprehensive approach

The researchers plan to take a comprehensive approach by identifying all the genes expressed in the glomerulus and characterising the proteins that regulate its function and the aberrations that arise with disease.

"We hope to be able to learn how glomerulus function is regulated and how vital proteins integrate with each other and their surroundings," says Professor Karl Tryggvason of Karolinska Institutet, coordinator of the project. "We need to understand these pathogenic mechanisms if the pharmaceutical industry is to develop effective drugs."

Possible therapeutic targets

The groups have already uncovered the causes of a number of rare kidney diseases, whereupon they described several proteins that are specific to the glomerulus and demonstrated their significance to glomerular development and function.

"Glomeruli contain unique cell types that have highly specialised functions," says co-applicant Professor Christer Betsholtz from Uppsala University and Karolinska Institutet. "The analyses we've done so far show that a large number of genes are specifically expressed here. We're now doing systematic analyses of their function in animal models. At the same time, we're identifying changes in gene expression in the glomeruli of patients with kidney disease. Taken together, the results give an indication of the signal systems and cellular functions that could serve as candidates for therapeutic targets."