Abstract P224: The Role Of Gata3 In Renin Cell Identity

Renin cells act as precursors cells of the kidney vasculature and show high plasticity in postnatal life in response to challenges to homeostasis. Our scRNA-seq studies revealed that the dual-zinc finger transcription factor Gata3, important for cell lineage commitment and differentiation inseveral tissues, is expressed in mouse renin cells. We found an enhancer associated with Gata3 in renin cells leading us to hypothesize that GATA3 is important for renin cell identity. We studied 60 and 120-day-old mice carrying a conditional deletion of Gata3 in renin cells: Gata3 fl/fl ;Ren1 dCre/+ ( Gata3-cKO ) and control Gata3 fl/fl ;Ren1 d+/+ . BUN and plasma renin levels were measured from blood samples collected by cardiac puncture. Ren1, Acta2, and Gata3 were visualized in kidney sections by immunostaining. Histological analysis was performed with H&E, PAS, or Masson’s Trichrome chemical reactions. The juxtaglomerular area (JGA) index was calculated as a ratio of renin-positive JGAs per the total number of glomeruli. Gata3-cKO mice have: 1) a marked reduction in Gata3 staining; 2) a marked reduction of Ren1 (1.78 ± 0.51 (n=5) vs. 12.96 ± 2.29 (n=6), p=.0006) and Akr1b7 (2.12 ± 0.35 (n=5) vs. 19.75 ± 5.43 (n=7), p<0.0001) mRNAs compared to controls under threat; 3) a significant decrease in circulating plasma renin compared to controls under basal conditions (15609 ± 14281 pg/ml (n=5) vs. 78778 ± 33925 pg/ml (n=7), p=.0039) and physiological threat (265981 ± 79431 vs. 62347 ± 75631 pg/ml (n=5), p=.0032); 4) a significantly reduced JGA index (28.47 ± 2.32 (n=5) vs. 44.42 ± 2.72 (n=5), p=.0001); 5) flattened JG cells with misplaced renin staining in the Bowman’s capsule; 6) renal abnormalities with evidence of glomerular sclerosis/fibrosis, hemorrhage with aneurysms, and evidence of inflammatory cell infiltration; 7) misplaced Acta2 staining in the intraglomerular mesangium, interstitium, and Bowman’s capsule. Our results suggest a role of Gata3 in the identity of cells of the renin lineage.