Majid Askaripour - Department of Physiology and Pharmacology, and Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
Hamid Najafipour - Department of Physiology and Pharmacology, and Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
Shadan Saberi - Department of Physiology and Pharmacology, Afzalipour Medical Faculty and Physiology Research Centre, Kerman University of Medical Sciences, Kerman, Iran
Saleh Yazdani - VIB-KU Leuven Center for Microbiology, Leuven, Belgium
Saeideh Jafarinejad-Farsangi - Physiology Research Centre, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
Soodeh Rajabi - Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
Elham Jafari - Pathology and Stem Cell Research Center, Department of Pathology, Kerman University of Medical Sciences, Kerman, Iran
Paul Proost - Laboratory of Molecular Immunology, Department of Microbiology, Immunology, and Transplantation, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium
Sofie Struyf - Laboratory of Molecular Immunology, Department of Microbiology, Immunology, and Transplantation, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium
Fariba Poosti - Laboratory of Molecular Immunology, Department of Microbiology, Immunology, and Transplantation, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium

Objective(s): Chronic kidney disease (CKD), accompanied by renal dysfunction, fibrosis, and apoptosis, is highly prevalent in postmenopausal women. We tested the hypothesis that isoflavone daidzein may ameliorate renal dysfunction and fibrosis through angiotensin II type ۱ (AT۱R) and angiotensin ۱-۷ (MasR) receptors in association with microRNAs ۳۳a and ۲۷a.Materials and Methods: Two weeks before the initiation of the experiments, rats (n=۸۴) underwent ovariectomy (OVX). Then, unilateral ureteral obstruction (UUO) was performed in OVX rats, and animals were allocated to the following groups (n=۲۱): sham vehicle (dimethyl sulfoxide; DMSO ۱%), UUO vehicle, UUO+۱۷β-estradiol (E۲), and UUO+daidzein. Each group encompassed three subgroups (n=۷) treated with saline, A۷۷۹ (MasR antagonist), or losartan (AT۱R antagonist) for ۱۵ days. The fractional urine excretion of sodium (FENa+) and potassium (FEK+), renal failure index (RFI), renal interstitial fibrosis (RIF index), glomerulosclerosis, miR-۳۳a, and miR-۲۷a expressions and their target genes were analyzed. Apoptosis was measured via cleaved caspase-۳ immunohistochemistry.Results: UUO increased kidney weight, FENa+, FEK+, urine calcium, RFI, RIF index, glomerulosclerosis, and cleaved caspase-۳. Moreover, expression of renal miR-۳۳a and miR-۲۷a, collagen۳A۱ mRNA, and protein were up-regulated post-UUO. Daidzein treatment alleviated the harmful effects of UUO especially in co-treatment with losartan. They also masked the anticipated worsening effects of A۷۷۹ on UUO.Conclusion: Compared with E۲, daidzein efficiently ameliorated renal dysfunction, fibrosis, and apoptosis through modulation of miR-۳۳a and miR-۲۷a expression and their crosstalk with AT۱R and MasR. Therefore, daidzein might be a promising candidate for treating CKD in postmenopausal and older women. 

Angiotensin receptor, Apoptosis, Daidzein, microRNAs, Ovariectomy, Renal fibrosis