Abstract
The incidence and prevalence of chronic kidney disease are constantly increasing and represent a major for public health. Renal failure is a complex mechanism involving a crosstalk between agents promoting renal inflammation and renal fibrosis. Because DDR1 is capable of participating to both, inflammation and fibrosis, investigations were carried out to test whether it can be a mediator of the progression of renal disease. To this end, a variety of experimental models of nephropathy each aggressing a different compartment of the kidney (vessels, tubular epithelium, and glomeruli) were applied to mice lacking expression of DDR1. In all tested models, DDR1 was induced in the corresponding renal compartment immediately after the disease and this local overexpression was accompanied by the activation of several proinflammatory and profibrotic pathways. In contrast, in DDR1 null animals these pathways were not activated which resulted to an impressive preservation of renal function and structure. Further proof of evidence came from experiments with in vivo administration of antisense oligonucleotides against DDR1. The fact that this pharmacogenetic approach protected animals against the development of renal disease further supports the hypothesis that DDR1 blockade can be a future treatment for renal disease, an incurable today human pathology.
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Chatziantoniou, C., Dorison, A., Dussaule, JC. (2016). DDR1 in Renal Function and Disease. In: Fridman, R., Huang, P. (eds) Discoidin Domain Receptors in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-6383-6_15
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DOI: https://doi.org/10.1007/978-1-4939-6383-6_15
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