Multi-omics Study Identifies c-Jun as Key Driver of Diabetic Kidney Disease
Researchers used an integrated multi-omics approach to map the molecular landscape of diabetic nephropathy in human tissue, identifying the transcription factor c-Jun as a central regulator of tubular injury and fibrosis. The study combined single-cell imaging, spatial transcriptomics, RNA sequencing, and chromatin profiling to characterize cell types, immune-fibrotic interactions, and gene regulatory networks in diseased kidneys. The findings suggest c-Jun could be a therapeutic target for slowing kidney disease progression in diabetic patients.
A new preprint study published on bioRxiv presents a comprehensive multi-omics atlas of diabetic nephropathy (DN), a leading cause of end-stage renal disease worldwide. By integrating single-cell multiplexed protein imaging, spatial transcriptomics, single-nucleus and single-cell RNA sequencing, and chromatin accessibility profiling, the researchers precisely mapped kidney cell types, their spatial distributions, and the molecular networks underlying tubular injury and fibrosis. The analysis identified eight distinct cellular neighborhoods that define the immune-fibrotic microenvironment of the diabetic kidney. The transcription factor c-Jun, encoded by the JUN gene, emerged as a master regulator of transcriptional reprogramming in injured tubular cells. Experiments in a diabetic mouse model confirmed c-Jun activation in injured proximal tubules, and an inducible mouse model demonstrated that tubular-specific c-Jun activation alone is sufficient to cause tubular injury, chronic inflammation, progressive fibrosis, and systemic metabolic disruptions including impaired glucose homeostasis. The study also found reduced expression of SLC4A4, a bicarbonate transporter critical for proximal tubular function, in injured tissue. Together, these findings provide a spatially resolved mechanistic framework for DN pathogenesis and nominate c-Jun as a potential therapeutic target.
What's missing
As a preprint, this study has not yet undergone formal peer review, and its findings should be interpreted with caution. The study does not address whether pharmacological inhibition of c-Jun in vivo can reverse or prevent DN progression. The translational relevance of the mouse model findings to human DN also remains to be validated in larger clinical cohorts.
What different sources said
- bioRxivCenter
A multi-omics map of diabetic nephropathy links c-Jun activation to tubular injury and metabolic stress
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