Translational profiles of proximal tubule during UUO

Injury to the proximal tubule can initiate chronic kidney disease and rates of progression are approximately 50% faster in males compared to females. The precise transcriptional changes in this nephron segment during fibrosis, and potential differences between sexes, remain undefined. We generated mice with proximal tubule-specific expression of an L10a ribosomal subunit protein fused with eGFP. We performed unilateral ureteral obstruction (UUO) surgery on male (n = 4) and female (n = 3) mice, collected proximal tubule-specific and bulk cortex mRNA at day 5 or 10 and sequenced to a depth of 30 million reads. Computational methods were applied to identify both sex-biased and shared molecular responses to fibrotic injury, including up- and down-regulated long non-coding RNAs and transcriptional regulators. Critical genes and pathways were validated by in situ hybridization.