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Hyperglycemia up‐regulates AT2 receptors via IRF‐1 in proximal tubule epithelial cells.
Author(s) -
Ali Quaisar,
Hussain Tahir
Publication year - 2010
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.24.1_supplement.585.8
Subject(s) - irf1 , medicine , receptor , endocrinology , messenger rna , biology , chemistry , natriuresis , microbiology and biotechnology , gene expression , kidney , gene , biochemistry
We have reported that the renal AT2 receptor expression and their function on natriuresis are increased in hyperglycemic obese rats. However, role of hyperglycemia and the mechanism responsible for increase in AT2 receptor expression is not known. The present study was designed to test the hypothesis that hyperglycemia increases AT2 receptor expression by transcriptional activation via interferon regulatory factor 1 (IRF1) in the renal proximal tubules. Western blotting and qRT‐PCR studies revealed that AT2 and IRF1 protein/mRNA expression in the proximal tubule (PTs) of obese rats was greater than in lean rats. To study the cause‐effect relationship, we used HK‐2 cells. Twenty hr incubation of HK2 cells with high glucose concentration (25 mM) caused an increase in the AT2 receptor protein/mRNA and the IRF1 expression. To study the role of IRF1 in hyperglycemia‐induced AT2 expression, we knocked‐down IRF1 using IRF1 siRNA (100 nM). Treatment with siRNA decreased IRF1 as well as AT2 receptor expression and prevented high glucose‐induced increase in the expression of both the IRF1 and AT2 receptor. The data suggest that hyperglycemia induces a transcriptional up‐regulation of AT2 receptor expression via increasing the IRF1 expression. This mechanism may be compensatory to promote natriuresis and prevent blood pressure increase in obese rats, as shown earlier.