Abstract P113: SOX6 IS NOT A RELEVANT TRANSCRIPTION FACTOR FOR RENIN TRANSCRIPTIONAL REGULATION BY JUXTAGLOMERUALR CELLS

The SRY (sex determining region Y)-box 6, Sox6 , encodes a member of trancription factors (TFs) crucial for organogenesis. It has been suggested that Sox6 is essential for the Renin transcriptional regulation. However, we identified Sox6 expression only in tubular cells. We aim to investigate whether Sox6 contributes to Renin gene expression by the Juxtaglomerular Cells in normal and under stress. Therefore, we generated Ren1 d -Cre;Sox6 -/- mice, where cells expressing Renin lacks the Sox6 gene. We randomized the mice into four groups (n= 6/group): Wild-type (WT) and mutants ( Sox6 cKO) exposed to either regular salt diet or low salt diet and captopril (0.5 mg/mL in water ad libitum for 8 days). The later condition decreases blood pressure and increases Renin transcription and exocytosis. We measured the blood pressure by direct carotid artery catheterization. There were no differences between WT and cKO in mean blood, systolic or diastolic pressures. ELISA assay measured the plasmatic Renin content, without significance in any group (WT: 126775 pg/mL ± 59035; cKO: 200008 pg/mL ± 68556; n=3). In sytu hybridization ( ISH ) for Sox6 has never been visible in the kidney despite all optimizations. Renin ISH had usual distribution in the Juxtaglomerular Apparatus (JGA; n=6). In the captopril treated groups, Renin intensity was higher and no differences were noted. Immunohistochemistry for Renin also reavealed no differences between WT and cKO. Yet, the renin+ cells extended along the afferent arterioles in the captopril treated groups. We calculated the Juxtaglomerular Index, which is the total number of renin+ JGA divided by all glomeruli. WT showed 156 renin+ JGA of 441 glomeruli (n=3), while the cKO exhibited 173 of 449 glomeruli (n=3). In the captopril groups, WT had 302 of 452 glomeruli (n=3), while the ckO exhibited a subtle decrease, 176 of 312 glomeruli (n=4), but without significance. Quantitative RT-PCR from the kidneys showed an increase in the relative R enin gene expression to s14 in cKO group (WT: 1.2 ± 0.8; cKO: 2.1 ± 2.2; n=3), while Sox6 relative gene expression to s14 decreased (WT: 1.02 ± 0.27; cKO: 0.35 ± 0.2; n=3). We conclude that Sox6 is not an important TF for Renin transcriptional regulation by JuxtaGlomerular Cells in neither normal nor stressed conditions.