Abstract
Renin expressing cells in the kidney’s juxta-glomeruluar compartment likely also serve as progenitors for adult glomerular cells in disease. Although these cells of renin lineage (CoRL) decrease in number with advancing kidney age, accompanied by less responsiveness to typical stimuli such as ACE-inhibition, mechanisms and the impact of sex as a biological variable with age are not known. Accordingly, labeled CoRL were sorted from individual young (2m) and aged (27m) male and female Ren1cCre|ZsGreen reporter mice, and their transcriptomic profiles analyzed by RNA seq. When both aged female and male mice were combined, there were 48 differentially expressed genes (DEG) compared to young mice. However, when compared to their young sex-matched mice, aged female and male mice had 159 and 503 DEGs respectively. In addition to marked differences in individual genes between aged female and male mice, gene ontology analysis showed major pathway differences by sex. The majority of DEGs in one sex did not significantly change or changed in the opposite direction in the other sex. These results show that in CoRL of advanced age, individual genes and gene ontologies change, but differ between female and male mice, highlighting sex related differences the aging process.
Highlights
With the global population living longer, increasing attention is focusing on the impact of advanced age on organ function, and how this might impact normal biological processes and pathways
Effect of age on the global transcriptomic changes in cells of renin lineage We hypothesized that with advancing age, cells of renin lineage (CoRL) have reduced stemness, accompanied by a reduced ability to proliferate and migrate from the juxta-glomerular compartment to the intra-glomerular compartment, with increased cell death compared to young mice
48 genes (FDR
Summary
With the global population living longer, increasing attention is focusing on the impact of advanced age on organ function, and how this might impact normal biological processes and pathways. Because of their biological functions in blood pressure and sodium regulation, changes to the cells of renin lineage (CoRL) have characteristically been considered of major functional importance with increasing kidney age. Healthy kidney aging is considered a hypo-reninemic state, based on lower plasma renin activity in human [315], and rats [16,17,18,19,20], reduced renin content in kidneys [16, 17, 20, 21], and reduced responsiveness to certain stimuli known to increase renin [3,4,5,6, 8, 16, 21, 22].
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