Basement membrane turnover and circulating matrix biomarkers in kidney disease
Chronic kidney disease (CKD) is characterised by kidney fibrosis and represents a major public health concern. Alport syndrome, a common monogenic cause of kidney failure caused by genetic variants in the type IV collagen genes COL4A3, COL4A4or COL4A5, leads to abnormal basement membrane remodelling and kidney fibrosis. Understanding the dynamics and mechanisms of kidney matrix remodelling is crucial for directing emerging gene therapies and developing non-invasive biomarkers to detect and stage kidney fibrosis earlier, ultimately enabling risk stratification and timely intervention. To define the temporal and spatial dynamics of kidney matrix remodelling, we applied a multi-omics strategy in a Col4a5-/-mousemodel of X-linked Alport syndrome, integrating stable isotope metabolic labelling, deep proteomicprofiling, bulk RNA sequencing, super-resolution imaging, and bioinformatic prediction.Transcriptomic profiling identified enrichment of extracellular matrix degradation pathways and upregulation of matrix proteases. This being the RNA-seq component.
Chronic kidney disease (CKD) is characterised by kidney fibrosis and represents a major public health concern. Alport syndrome, a common monogenic cause of kidney failure caused by genetic variants in the type IV collagen genes COL4A3, COL4A4or COL4A5, leads to abnormal basement membrane remodelling and kidney fibrosis. Understanding the dynamics and mechanisms of kidney matrix remodelling is crucial for directing emerging gene therapies and developing non-invasive biomarkers to detect and stage kidney fibrosis earlier, ultimately enabling risk stratification and timely intervention. To define the temporal and spatial dynamics of kidney matrix remodelling, we applied a multi-omics strategy in a Col4a5-/-mousemodel of X-linked Alport syndrome, integrating stable isotope metabolic labelling, deep proteomicprofiling, bulk RNA sequencing, super-resolution imaging, and bioinformatic prediction.Transcriptomic profiling identified enrichment of extracellular matrix degradation pathways and upregulation of matrix proteases. This being the RNA-seq component.
European Bioinformatics Institute