Transcriptomic changes in glomeruli in response to a high salt challenge in the Dahl SS rat.

Salt sensitivity impacts a significant portion of the population and is an important contributor to the development of chronic kidney disease. One of the significant early predictors of salt-induced damage is albuminuria, which reflects the deterioration of the renal filtration barrier - the glomerulus. Despite significant research efforts, there is still a gap in knowledge regarding the molecular mechanisms and signaling networks contributing to instigating and/or perpetuating salt-induced glomerular injury. To address this gap, we used 8-week-old male Dahl Salt-Sensitive (SS) rats fed a normal (0.4% NaCl, NS) or challenged with a high salt diet (4% NaCl, HS) for 3 weeks. At the end of the protocol, a pure fraction of renal glomeruli obtained by differential sieving was used for next-generation RNA sequencing and comprehensive semi-automatic transcriptomic data analyses, which revealed 149 differentially expressed genes (107 and 42 were down- and up-regulated, respectively). Further, a combination of predictive gene correlation networks and computational bioinformatic analyses revealed pathways impacted by a HS dietary challenge, including renal metabolism, mitochondrial function, apoptotic signaling and fibrosis, cell cycle, inflammatory and immune responses, circadian clock, cytoskeletal organization, GPCR signaling, and calcium transport. In conclusion, we report here novel transcriptomic interactions and corresponding predicted pathways affecting glomeruli under salt-induced stress.