GSE117681
Next Generation Sequencing Facilitates Quantitative Analysis Of Wild Type And Epithelium-specific Cox10-/- Renal Transcriptomes
Description: We find multiple evidence that mitochondria are directly and indirectly involved in the pathologic activation of cellular innate immunity. Previously, studies have shown that pathologic type I interferon signatures promote autoimmune diseases and noted mitochondrial and mtDNA dysregulation in chronic inflammatory diseases. Based upon previous data from our lab and others, we anticipated a direct link between the mitochondrial dysfunction and the elevated production of type I interferon or the increase of other innate immune signatures in chronic and general inflammatory diseases. In this project, we wished to test our overall hypothesis that inhibition of mtDNA-mediated immune activation pathway is a promising pharmacological target for chronic inflammatory diseases. To pursue this goal, we developed a murine conditional knockout model, where kidney epithelial cells show dysfunctioning mitochondrial phenotype, and verified that this mouse model has lethal kidney failure with features of chronic kidney disease. By using systems biology approaches, we aimed to examine which genes are regulated in the kidney with dysfunctioning mitochondrial phenotype and identify the main pathways leading to the chronic autoimmune disease. Results: We found that interferon-stimulated genes are upregulated in Cox10 mouse kidney. Likely, mitochondrial dysregulation and mtDNA release induces expression of genes known as interferon-stimulated genes (IGS) (West et al., Nature 2015). Overall design: Renal mRNA profiles of 3-month old wild type (WT) and epithelial-specific Cox10-/- mice were generated by deep sequencing, in quadruplicate, on the Illumina HiSeq 2500 platform.