| چکیده انگلیسی مقاله |
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 1 (AT1R) and angiotensin 1-7 (MasR) receptors in association with microRNAs 33a and 27a.Materials and Methods: Two weeks before the initiation of the experiments, rats (n=84) underwent ovariectomy (OVX). Then, unilateral ureteral obstruction (UUO) was performed in OVX rats, and animals were allocated to the following groups (n=21): sham vehicle (dimethyl sulfoxide; DMSO 1%), UUO vehicle, UUO+17β-estradiol (E2), and UUO+daidzein. Each group encompassed three subgroups (n=7) treated with saline, A779 (MasR antagonist), or losartan (AT1R antagonist) for 15 days. The fractional urine excretion of sodium (FENa+) and potassium (FEK+), renal failure index (RFI), renal interstitial fibrosis (RIF index), glomerulosclerosis, miR-33a, and miR-27a expressions and their target genes were analyzed. Apoptosis was measured via cleaved caspase-3 immunohistochemistry.Results: UUO increased kidney weight, FENa+, FEK+, urine calcium, RFI, RIF index, glomerulosclerosis, and cleaved caspase-3. Moreover, expression of renal miR-33a and miR-27a, collagen3A1 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 A779 on UUO.Conclusion: Compared with E2, daidzein efficiently ameliorated renal dysfunction, fibrosis, and apoptosis through modulation of miR-33a and miR-27a expression and their crosstalk with AT1R and MasR. Therefore, daidzein might be a promising candidate for treating CKD in postmenopausal and older women. |
| نویسندگان مقاله |
| 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|Laboratory of Molecular Cell Biology, Department of Biology, KU Leuven, 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
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