Sex-Specificity of Mineralocorticoid Target Gene Expression during Renal Development, and Long-Term Consequences
نویسندگان
چکیده
Sex differences have been identified in various biological processes, including hypertension. The mineralocorticoid signaling pathway is an important contributor to early arterial hypertension, however its sex-specific expression has been scarcely studied, particularly with respect to the kidney. Basal systolic blood pressure (SBP) and heart rate (HR) were measured in adult male and female mice. Renal gene expression studies of major players of mineralocorticoid signaling were performed at different developmental stages in male and female mice using reverse transcription quantitative PCR (RT-qPCR), and were compared to those of the same genes in the lung, another mineralocorticoid epithelial target tissue that regulates ion exchange and electrolyte balance. The role of sex hormones in the regulation of these genes was also investigated in differentiated KC3AC1 renal cells. Additionally, renal expression of the 11 β-hydroxysteroid dehydrogenase type 2 (11βHSD2) protein, a regulator of mineralocorticoid specificity, was measured by immunoblotting and its activity was indirectly assessed in the plasma using liquid-chromatography coupled to mass spectrometry in tandem (LC-MSMS) method. SBP and HR were found to be significantly lower in females compared to males. This was accompanied by a sex- and tissue-specific expression profile throughout renal development of the mineralocorticoid target genes serum and glucocorticoid-regulated kinase 1 (Sgk1) and glucocorticoid-induced leucine zipper protein (Gilz), together with Hsd11b2, Finally, the implication of sex hormones in this sex-specific expression profile was demonstrated in vitro, most notably for Gilz mRNA expression. We demonstrate a tissue-specific, sex-dependent and developmentally-regulated pattern of expression of the mineralocorticoid pathway that could have important implications in physiology and pathology.
منابع مشابه
نگاهی به ژن درمانی، پیشرفتهای اخیر و چشم انداز آینده
Human gene therapy has attracted increasing attention as a highly encouraging therapeutic approach to treat wide variety of diseases, other than genetically inherited and monogenic disorders. This approach entails the introduction and expression of a variety of nucleic acids into human target cells for therapeutic purposes. In this article, we review the history, highlights, recently progresses...
متن کاملOptimization of Gene Expression Programming Model using Wavelet Transform for Simulating Long-term Rainfall in Anzali City
Due to drought and climate change, estimation and prediction of rainfall is quite important in various areas all over the world. In this study, a novel artificial intelligence (AI) technique (WGEP) was developed to model long-term rainfall (67 years period) in Anzali city for the first time. This model was combined using Wavelet Transform (WT) and Gene Expression Programming (GEP) model. Firstl...
متن کاملSkin manifestations of patients with chronic renal failure on long-term hemodialysis
Background: There are several reports of different cutaneous manifestations in patients with chronic renal failure (CRF) managed by repeated hemodialysis, in the literature. Objective: This study was conducted to evaluate the prevalence of skin manifestations in patients suffering from CRF who are on long-term hemodialysis. Patients and Methods: The skin manifestations of 108 CRF patients who u...
متن کاملEffect of Memantine on Expression of NAT-Rad18, Rad18 and Sorl1 Genes in Rat Model of Alzheimer\'s Disease
Background and Objective: Dysregulation of long-term expression of non-coding RNAs (lncRNAs) has a potential role in progressive brain disorders such as Alzheimer's disease. This study aimed to analyze the apoptosis and expression of 51A and NAT-Rad18 lncRNAs and their target genes in brain tissue and peripheral blood mononuclear cells (PBMCs) of the rat model of AD, before and after memantine ...
متن کاملMicroRNA-205 inhibits renal cells apoptosis via targeting CMTM4
Objective(s):MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression. They have important roles in kidney development, homeostasis and disease, and participate in the onset and progression of tubulointerstitial sclerosis and end-stage glomerular lesions that occur in various forms of chronic kidney disease (CKD). In the present study, we elucidated the role of microR...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 18 شماره
صفحات -
تاریخ انتشار 2017