Periostin and discoidin domain receptor 1: New biomarkers or targets for therapy of renal disease

Abstract

Chronic kidney disease (CKD) can be a life-threatening condition, which eventually requires renal replacement therapy through dialysis or transplantation. A lot of effort and resources have been invested the last years in the identification of novel markers of progression and targets for therapy, in order to achieve a more efficient prognosis, diagnosis, and treatment of renal diseases. Using experimental models of renal disease, we identified and studied two promising candidates: periostin, a matricellular protein with high expression in bone and dental tissues, and discoidin domain receptor 1 (DDR1), a transmembrane collagen receptor of the tyrosine kinase family. Both proteins are inactive in physiological conditions, while they are highly upregulated during development of renal disease and are primarily expressed at the sites of injury. Further studies demonstrated that both periostin and DDR1 are involved in the regulation of inflammation and fibrosis, two major processes implicated in the development of renal disease. Targeting of either protein by genetic deletion or pharmacogenetic inhibition via antisense oligonucleotides highly attenuates renal damage and preserves renal structure and function in several animal models. The scope of this review is to summarize the existing evidence supporting the role of periostin and DDR1 as novel biomarkers and therapeutic targets in CKD.