Unfavorable Reduction in the Ratio of Endothelin B to A Receptors in Experimental 5/6 Nephrectomy and Adenine Models of Chronic Renal Insufficiency

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Törmänen , S , Lakkisto , P , Eräranta , A , Kööbi , P , Tikkanen , I , Niemelä , O , Mustonen , J & Pörsti , I 2020 , ' Unfavorable Reduction in the Ratio of Endothelin B to A Receptors in Experimental 5/6 Nephrectomy and Adenine Models of Chronic Renal Insufficiency ' , International Journal of Molecular Sciences , vol. 21 , no. 3 , 936 . https://doi.org/10.3390/ijms21030936

Title: Unfavorable Reduction in the Ratio of Endothelin B to A Receptors in Experimental 5/6 Nephrectomy and Adenine Models of Chronic Renal Insufficiency
Author: Törmänen, Suvi; Lakkisto, Päivi; Eräranta, Arttu; Kööbi, Peeter; Tikkanen, Ilkka; Niemelä, Onni; Mustonen, Jukka; Pörsti, Ilkka
Other contributor: University of Helsinki, HUSLAB
University of Helsinki, HUS Abdominal Center







Date: 2020-02
Language: eng
Number of pages: 19
Belongs to series: International Journal of Molecular Sciences
ISSN: 1422-0067
DOI: https://doi.org/10.3390/ijms21030936
URI: http://hdl.handle.net/10138/315276
Abstract: Chronic renal insufficiency (CRI) is characterized by increased endothelin 1 (ET-1) synthesis. We studied rat kidney endothelin receptor A (ETA) and receptor B (ETB) expressions after 12 and 27 weeks of 5/6 nephrectomy, and after 12 weeks of 0.3% adenine diet, representing proteinuric and interstitial inflammation models of CRI, respectively. Uric acid and calcium-phosphate metabolism were modulated after 5/6 nephrectomy, while ETA blocker and calcimimetic were given with adenine. Endothelin receptor mRNA levels were measured using RT-qPCR and protein levels using autoradiography (5/6 nephrectomy) or ELISA (adenine model). Both 12 and 27 weeks after 5/6 nephrectomy, kidney cortex ETA protein was increased by similar to 60% without changes in ETB protein, and the ETB:ETA ratio was reduced. However, the ETB:ETA mRNA ratio did not change. In the adenine model, kidney ETA protein was reduced by similar to 70%, while ETB protein was suppressed by similar to 95%, and the ETB:ETA ratio was reduced by similar to 85%, both at the protein and mRNA levels. The additional interventions did not influence the observed reductions in the ETB:ETAratio. To conclude, unfavorable reduction in the ETB:ETA protein ratio was observed in two different models of CRI. Therefore, ETA blockade may be beneficial in a range of diseases that cause impaired kidney function.
Subject: chronic renal insufficiency
chronic kidney disease
endothelin receptor A
endothelin receptor B
creatinine
calcium
phosphate
uric acid
sitaxentan
cinacalcet
paricalcitol
ANGIOTENSIN-CONVERTING ENZYME
CHRONIC KIDNEY-DISEASE
PHOSPHATE-BINDING
GENE-EXPRESSION
MESSENGER-RNA
HYPERURICEMIA
GLOMERULOSCLEROSIS
HYPERTENSION
PARICALCITOL
SELECTIVITY
3111 Biomedicine
1182 Biochemistry, cell and molecular biology
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