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Male Mice Heterozygous LSD1 Knockout Gene Prevented the Effect of High Sodium Intake on Renal Fibrosis and AT1 Conformational Status
Author(s) -
Nascimento Mariana Moura,
Katayama Isis Akemi,
Pojoga Luminita H,
Heimann Joel Claudio
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.866.3
Subject(s) - medicine , chemistry , endocrinology , angiotensin ii , receptor , agonist , angiotensin ii receptor type 1 , knockout mouse
Aim To 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. Methods LSD1 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‐HETRenal Fibrosis (%) 1.08±0.03 * 1.13±0.04 1.14±0.03 * 1.20±0.03 1.23±0.02 1.22±0.02Glomerular Volume (×10 6 μm 3) 0.25±0.01 0.27±0.01 0.25±0.01 0.23±0.01 0.27±0.01 0.27±0.01Glomerular Diameter (μm) 82.4±1.78 84.3±2.92 84.0±1.63 81.0±1.31 84.1±1.58 84.7±2.98Conformational 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±0.67Conformational 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±0.38Data are reported as mean±SEM. * p<0.05 vs. HS‐WT and & p<0.05 vs. LS‐WTConclusions Interestingly, 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 Information Supported by FAPESP, CAPES and American Heart Association This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .