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.

Keywords: biomarkers; chronic kidney disease; discoidin domain receptor 1; periostin; therapeutic targets.

Figure 1

Mechanisms of induction and physiopathological actions of periostin during renal disease. Periostin can be induced by a variety of different growth factors, transcription factors, or signaling pathways (left), while its activation leads to stimulation of integrin signaling, matrix assembly, promotion of inflammatory pathways, and cell phenotype changes (right).

Figure 2

Mechanisms of discoidin domain receptor 1 (DDR1) activation and amplification of renal damage during chronic kidney disease. Collagen binding to DDR1 receptor dimers induces the receptor phosphorylation and activation, which stimulates pro-inflammatory and pro-fibrotic pathways creating a vicious circle of continuous renal damage.