Protective effects of genetic inhibition of Discoidin Domain Receptor 1 in experimental renal disease

Monique Kerroch, Carlo Alfieri, Aude Dorison, Jean Jacques Boffa, Christos Chatziantoniou, Jean Claude Dussaule

Research output: Contribution to journalArticlepeer-review

Abstract

Chronic kidney disease is a progressive incurable pathology affecting millions of people. Intensive investigations aim to identify targets for therapy. We have previously demonstrated that abnormal expression of the Discoidin Domain Receptor 1 (DDR1) is a key factor of renal disease by promoting inflammation and fibrosis. The present study investigates whether blocking the expression of DDR1 after the initiation of renal disease can delay or arrest the progression of this pathology. Severe renal disease was induced by either injecting nephrotoxic serum (NTS) or performing unilateral ureteral obstruction in mice, and the expression of DDR1 was inhibited by administering antisense oligodeoxynucleotides either at 4 or 8 days after NTS (corresponding to early or more established phases of disease, respectively), or at day 2 after ligation. DDR1 antisense administration at day 4 stopped the increase of proteinuria and protected animals against the progression of glomeruloneprhitis, as evidenced by functional, structural and cellular indexes. Antisense administration at day 8 delayed progression-but to a smaller degree-of renal disease. Similar beneficial effects on renal structure and inflammation were observed with the antisense administration of DDR1 after ureteral ligation. Thus, targeting DDR1 can be a promising strategy in the treatment of chronic kidney disease.

Original languageEnglish
Article number21262
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Feb 16 2016

ASJC Scopus subject areas

  • General

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