Single-cell transcriptional analysis of kidney from aging mice with podocyte specific RARRES1 overexpression

Retinoic acid receptor responder protein-1 (RARRES1) was identified as a podocyte transmembrane protein whose expression correlates with glomerular disease progression. The cytopathic effect of RARRES1 is carried out only when proteolytically cleaved in its ectodomain into a soluble form (sRARRES1) and subsequently endocytosed by podocytes, as a membrane-bound, cleavage site mutant failed to induce any effect. We investigated the effects of long-term podocyte-derived RARRES1 overexpression on aging-induced kidney injury. 18 months of mice with Nphs1-rtTA; TRE-hRARRES1WT transgenes and control littermates were fed with doxycycline-supplemented chow for 16 months. PBS-perfused mouse kidneys were harvested and single-cells were prepared.