Male Mice Heterozygous LSD1 Knockout Gene Prevented the Effect of High Sodium Intake on Renal Fibrosis and AT1 Conformational Status

Abstract

AimTo evaluate the effects of dietary salt overload or restriction on renal structure and AT1 conformational status in wild type and LSD1 (lysine specific demethylase 1) deficient mice.MethodsLSD1 deficient (Het) and wild type (WT) mice were maintained on high (HS), low (LS) or normal (NS) sodium intake, for 12 months. Renal fibrosis, glomerular volume, glomerular diameter and AT1 and AT2 receptor conformational status (activated or not activated by agonist ligation) were evaluated at the end of the study.Results: (n=6–17/group) LS‐WT LS‐HET NS‐WT NS‐HET HS‐WT HS‐HET Renal Fibrosis (%) 1.08±0.03* 1.13±0.04 1.14±0.03* 1.20±0.03 1.23±0.02 1.22±0.02 Glomerular Volume (×106 μm3) 0.25±0.01 0.27±0.01 0.25±0.01 0.23±0.01 0.27±0.01 0.27±0.01 Glomerular Diameter (μm) 82.4±1.78 84.3±2.92 84.0±1.63 81.0±1.31 84.1±1.58 84.7±2.98 Conformational Status AT1R (FI) 16.9±0.81 19.8±1.43 18.8±0.83 21.2±2.10 19.8±0.84& 21.4±0.67 Conformational Status AT2R (FI) 7.08±0.33 7.27±0.38 6.71±0.28 7.12±0.50 7.69±0.32 6.97±0.38 Data are reported as mean±SEM. p<0.05 vs. HS‐WT and p<0.05 vs. LS‐WT ConclusionsInterestingly, high salt intake stimulated renal fibrosis only in WT mice. The same phenomenon was observed in AT1 conformational status. In addition, the dietary salt content did not influence the glomerular volume and diameter in both WT and Het models suggesting that: renal fibrosis development and AT1 conformational status in response to dietary salt overload occur through different mechanisms in WT and Het animals stimulating further studies to elucidate this phenomenon.Support or Funding InformationSupported by FAPESP, CAPES and American Heart AssociationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.