Research Article: Sex differences in transcriptomic profiles in aged kidney cells of renin lineage

Date Published: April 18, 2018

Publisher: Impact Journals

Author(s): Yuliang Wang, Diana G. Eng, Jeffrey W. Pippin, Sina A. Gharib, Aaron McClelland, Kenneth W. Gross, Stuart J. Shankland.


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.

Partial Text

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. Recent studies have shown functional and structural changes in the healthy aged kidney, and how these changes might impact outcomes in glomerular and tubulointerstitial diseases [1,2]. For example, 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.

Recent studies have shown that in addition to cells of renin lineage (CoRL) serving a major endocrine function, they likely also have a major biological role serving as progenitors for adult mesangial cells, podocytes, glomerular parietal epithelial cells and pericytes [23,41–44,68]. Advanced aging is accompanied by reduced renin content in CoRL [3,10,74], and decreased CoRL number in aged mice [23]. In addition, CoRL proliferation in aged mice is blunted in response to ACE-inhibitors [21]. Because gene expression in CoRL might provide insights into potential mechanisms for changes during aging, we performed RNAseq on sorted CoRL to define changes in their transcriptional profile in aged mice compared to young age mice. Overall sex also had a major impact in gene patterns with advanced age.




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