title: Protective effects of genetic inhibition of Discoidin Domain Receptor 1 in experimental renal disease.
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.
authors.affiliation: INSERM UMR S 1155, Hôpital Tenon, 75020 Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, Paris, France.
authors.forename: Monique
authors.initials: M
authors.lastname: Kerroch
authors.affiliation: INSERM UMR S 1155, Hôpital Tenon, 75020 Paris, France.|Department of Medicine and Medical Specialties, Unit of Nephrology, Dialysis, and Renal Transplant, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Alfieri
authors.affiliation: INSERM UMR S 1155, Hôpital Tenon, 75020 Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, Paris, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Dorison
authors.affiliation: INSERM UMR S 1155, Hôpital Tenon, 75020 Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, Paris, France.|Service de Néphrologie et Dialyses, Hôpital Tenon, AP-HP, Paris, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Boffa
authors.affiliation: INSERM UMR S 1155, Hôpital Tenon, 75020 Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, Paris, France.
authors.forename: Christos
authors.initials: C
authors.lastname: Chatziantoniou
authors.affiliation: INSERM UMR S 1155, Hôpital Tenon, 75020 Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, Paris, France.|Department of Physiology, Saint-Antoine Hospital, AP-HP, Paris, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Dussaule
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D016373:DNA, Antisense / Q000008:administration & dosage; D000070819:Discoidin Domain Receptor 1 / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005355:Fibrosis; D015870:Gene Expression; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D007674:Kidney Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice
chemical_list: D016207:Cytokines; D016373:DNA, Antisense; D018836:Inflammation Mediators; D000070819:Discoidin Domain Receptor 1