TY - JOUR
T1 - Transcriptomic changes in glomeruli in response to a high salt challenge in the Dahl SS rat
AU - Semenikhina, Marharyta
AU - Lysikova, Daria V.
AU - Spires, Denisha R.
AU - Domondon, Mark
AU - Stadler, Krisztian
AU - Palygin, Oleg
AU - Ilatovskaya, Daria V.
N1 - Publisher Copyright:
© 2024 the American Physiological Society.
PY - 2024/1
Y1 - 2024/1
N2 - Salt sensitivity impacts a significant portion of the population and is an important contributor to the development of chronic kidneydisease. 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 molecularme chanisms and signaling networks contributing to instigating and/or perpetuating salt-induced glomerular injury. To address this gap, we used 8-wk-old male Dahl salt-sensitive rats fed a normal-salt diet (0.4% NaCl) or challenged with a high-salt diet (4%NaCl) for 3 wk. At the end of the protocol, a pure fraction of renal glomeruli obtained by differential sieving was used for nextgeneration RNA sequencing and comprehensive semi-automatic transcriptomic data analyses, which revealed 149 differentially expressed genes (107 and 42 genes were down regulated and up regulated, respectively). Furthermore, a combination of predictivegene correlation networks and computational bio informatic analyses revealed pathways impacted by a high salt dietary challenge, including renal metabolism, mitochondrial function, apoptotic signaling and fibrosis, cell cycle, inflammatory and immune responses, circadian clock, cytoskeletal organization, G protein-coupled receptor signaling, and calcium transport. In conclusion, we report here novel transcriptomic interactions and corresponding predicted pathways affecting glomeruli under salt-inducedstress. NEW & NOTEWORTHY Our study demonstrated novel pathways affecting glomeruli under stress induced by dietary salt. Predictive gene correlation networks and bioinformatic semi-automatic analysis revealed changes in the pathways relevant to mitochondrialfunction, inflammatory, apoptotic/fibrotic processes, and cell calcium transport.
AB - Salt sensitivity impacts a significant portion of the population and is an important contributor to the development of chronic kidneydisease. 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 molecularme chanisms and signaling networks contributing to instigating and/or perpetuating salt-induced glomerular injury. To address this gap, we used 8-wk-old male Dahl salt-sensitive rats fed a normal-salt diet (0.4% NaCl) or challenged with a high-salt diet (4%NaCl) for 3 wk. At the end of the protocol, a pure fraction of renal glomeruli obtained by differential sieving was used for nextgeneration RNA sequencing and comprehensive semi-automatic transcriptomic data analyses, which revealed 149 differentially expressed genes (107 and 42 genes were down regulated and up regulated, respectively). Furthermore, a combination of predictivegene correlation networks and computational bio informatic analyses revealed pathways impacted by a high salt dietary challenge, including renal metabolism, mitochondrial function, apoptotic signaling and fibrosis, cell cycle, inflammatory and immune responses, circadian clock, cytoskeletal organization, G protein-coupled receptor signaling, and calcium transport. In conclusion, we report here novel transcriptomic interactions and corresponding predicted pathways affecting glomeruli under salt-inducedstress. NEW & NOTEWORTHY Our study demonstrated novel pathways affecting glomeruli under stress induced by dietary salt. Predictive gene correlation networks and bioinformatic semi-automatic analysis revealed changes in the pathways relevant to mitochondrialfunction, inflammatory, apoptotic/fibrotic processes, and cell calcium transport.
KW - Dahl salt-sensitive rat
KW - glomerulus
KW - high-salt diet
KW - transcriptomics
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U2 - 10.1152/physiolgenomics.00075.2023
DO - 10.1152/physiolgenomics.00075.2023
M3 - Article
C2 - 37955135
AN - SCOPUS:85180637633
SN - 1094-8341
VL - 56
SP - 98
EP - 111
JO - Physiological Genomics
JF - Physiological Genomics
IS - 1
ER -