Skip to Main content Skip to Navigation
Journal articles

Genetic inhibition of discoidin domain receptor 1 protects mice against crescentic glomerulonephritis.

Abstract : This study investigated the role of discoidin domain receptor 1 (DDR1), a collagen receptor that displays tyrosine-kinase activity, in the development of glomerulonephritis. Crescentic glomerulonephritis was induced in DDR1-deficient mice and their wild-type (WT) littermates as controls, by injection of alloimmune sheep nephrotoxic serum (NTS). Histological, functional and transcriptomic studies were performed. Glomerulonephritis produced a 17-fold increase of DDR1 expression, predominantly in glomeruli. DDR1 deletion protected NTS-treated mice against glomerular disease (proteinuria/creatininuria 5.5±1.1 vs. 13.2±0.8 g/mmol in WT, crescents 12±2 vs. 24±2% of glomeruli, urea 16±2 vs. 28±5 mM), hypertension (123±11 vs. 157±8 mmHg), and premature death (70 vs. 10% survival) (all P<0.05). Reciprocal stimulation between DDR1 and interleukin-1b expression in vivo and in cultured podocytes suggested a positive feed-back loop between DDR1 and inflammation. In NTS-treated WT mice, administration of DDR1-specific antisense oligodeoxynucleotides decreased DDR1 expression (-56%) and protected renal function and structure, including nephrin expression (4.2±1.4 vs. 0.9±0.4 arbitrary units, P<0.05), compared to control mice receiving scrambled oligodeoxynucleotides. The therapeutic potential of this approach was reinforced by the observation of increased DDR1 expression in glomeruli of patients with lupus nephritis and Goodpasture's syndrome. These results prompt further interest in DDR1 blockade strategies, especially in the treatment of glomerulonephritis.
Document type :
Journal articles
Complete list of metadata

Cited literature [45 references]  Display  Hide  Download
Contributor : Pierre Ronco Connect in order to contact the contributor
Submitted on : Monday, December 16, 2013 - 1:13:19 PM
Last modification on : Sunday, June 26, 2022 - 1:19:44 AM
Long-term archiving on: : Saturday, April 8, 2017 - 6:46:26 AM


 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document



Monique Kerroch, Dominique Guerrot, Sophie Vandermeersch, Sandrine Placier, Laurent Mesnard, et al.. Genetic inhibition of discoidin domain receptor 1 protects mice against crescentic glomerulonephritis.. FASEB Journal, Federation of American Society of Experimental Biology, 2012, 26 (10), pp.4079-91. ⟨10.1096/fj.11-194902⟩. ⟨inserm-00919121⟩



Record views