PRJNA721721
Mus musculus Transcriptome - Investigation of ASOs targeting Ddit3 (CHOP) in diabetic kidney disease
The ER-stress response and in particular the maladaptive and cell-death-promoting transcription factor CCAAT/Enhancer-Binding Protein Homologous Protein (CHOP) have been linked with diabetic kidney disease. Specific therapies targeting maladaptive ER-stress signaling are missing. Here we show that an antisense-oligonucleotide-based approach specifically reducing CHOP expression ameliorates diabetic kidney disease in mice, providing renal protection on top of ACE-inhibition. CHOP-inhibition improves parameters of both glomerular and tubular damage. This establishes that ASO-based therapies constitute a potentially new therapeutic approach targeting specifically maladaptive ER-stress signaling and improving diabetic kidney disease.